In the 1880s, in Hawaii, a Californian physician working at a hospital for lepers injected twelve girls under the age of 12 with syphilis.

In 1895, the New York pediatrician Henry Heiman intentionally infected two "idiots" (mentally disabled boys)—one four-year-old and one sixteen-year old—with gonorrhea as part of a medical experiment. A review of the medical literature of the late 19th and early 20th centuries found that there were more than 40 reports of experimental infections with gonorrheal culture, including some where gonorrheal organisms were applied to the eyes of sick children.

In 1900, U.S Army doctors in the Philippines infected five prisoners with bubonic plague and induced beriberi in 29 prisoners; four of the test subjects died as a result. In 1906, Professor Richard Strong of Harvard University intentionally infected 24 Filipino prisoners with cholera, which had somehow become contaminated with plague. He did this without the consent of the patients, and without informing them of what he was doing. All of the subjects became sick and 13 died.

In 1908, three Philadelphia researchers infected dozens of children with tuberculin at the St. Vincent's House orphanage in Philadelphia, causing permanent blindness in some of the children and painful lesions and inflammation of the eyes in many of the others. In the study they refer to the children as "material used".

In 1909, F. C. Knowles released a study describing how he had deliberately infected two children in an orphanage with Molluscum contagiosum after an outbreak in the orphanage, in order to study the disease.

In 1911, Dr. Hideyo Noguchi of the Rockefeller Institute for Medical Research injected 146 hospital patients (some of whom were children) with syphilis. He was later sued by the parents of some of the child subjects, who allegedly contracted syphilis as a result of his experiments.

In 1931 Cornelius Rhoads, also of the Rockefeller Institute, claimed to have injected cancer cells into Puerto Ricans. He later claimed he was joking and was acquitted.

The Tuskegee syphilis experiment was a clinical study conducted between 1932 and 1972 in Tuskegee, Alabama, by the U.S. Public Health Service. In the experiment, 400 impoverished black males who had syphilis were offered "treatment" by the researchers, who did not tell the test subjects that they had syphilis and did not give them treatment for the disease. By 1947, penicillin became available as treatment, but those running the study prevented study participants from receiving treatment elsewhere, lying to them about their true condition, so that they could observe the effects of syphilis on the human body. By the end of the study in 1972, only 74 of the test subjects were alive. 28 of the original 399 men had died of syphilis, 100 were dead of related complications, 40 of their wives had been infected, and 19 of their children were born with congenital syphilis. The study was not shut down until 1972, when its existence was leaked to the press, forcing the researchers to stop in the face of a public outcry.

In 1941, at the University of Michigan, doctors Francis and Jonas Salk and other researchers deliberately infected patients at several Michigan mental institutions with the influenza virus by spraying the virus into their nasal passages. Francis Rous, editor of the Journal of Experimental Medicine wrote the following to Francis regarding the experiments:

"It may save you much trouble if you publish your paper ... elsewhere than in the Journal of Experimental Medicine. The Journal is under constant scrutiny by the anti-vivisectionists who would not hesitate to play up the fact that you used for your tests human beings of a state institution. That the tests were wholly justified goes without saying."

In 1941 Dr. William C. Black inoculated a twelve month old baby "offered as a volunteer" with herpes. He submitted his research to The Journal of Experimental Medicine and it was rejected on ethical grounds. The editor of the Journal of Experimental Medicine, Francis Payton Rous, called the experiment "an abuse of power, an infringement of the rights of an individual, and not excusable because the illness which followed had implications for science." It was later published in the Journal of Pediatrics.

The Stateville Penitentiary Malaria Study was the site of a controlled study of the effects of malaria on the prisoners of Stateville Penitentiary near Joliet, Illinois beginning in the 1940s. The study was conducted by the Department of Medicine at the University of Chicago in conjunction with the United States Army and the State Department. At the Nuremberg trials, Nazi doctors cited the malaria experiments as part of their defense. The study continued at Stateville Penitentiary for 29 years. In related studies from 1944 to 1946, Dr. Alf Alving, a professor at the University of Chicago Medical School, purposely infected psychiatric patients at the Illinois State Hospital with malaria, so that he could test experimental malaria treatments on them.

In a 1946 to 1948 study in Guatemala, U.S. researchers used prostitutes to infect prison inmates, insane asylum patients, and Guatemalan soldiers with syphilis and other sexually transmitted diseases, in order to test the effectiveness of penicillin in treating sexually transmitted diseases. They later tried infecting people with "direct inoculations made from syphilis bacteria poured into the men's penises and on forearms and faces that were slightly abraded . . . or in a few cases through spinal punctures". Approximately 700 people were infected as part of the study (including orphan children). The study was sponsored by the Public Health Service, the National Institutes of Health and the Pan American Health Sanitary Bureau (now the World Health Organization's Pan American Health Organization) and the Guatemalan government. The team was led by John Charles Cutler, who later participated in the Tuskegee syphilis experiments. Cutler chose to do the study in Guatemala because he would not have been permitted to do it in the United States.

In 1950, in order to conduct a simulation of a biological warfare attack, the U.S. Navy used airplanes to spray large quantities of the bacteria Serratia marcescens – considered harmless at this time – over the city of San Francisco, which caused numerous citizens to contract pneumonia-like illnesses, and killed at least one person. The family of the man who was killed sued for gross negligence, but a federal judge ruled in favor of the government in 1981.Serratia tests were continued until at least 1969.

Also in 1950, Dr. Joseph Stokes of the University of Pennsylvania deliberately infected 200 female prisoners with viral hepatitis.

From the 1950s to 1972, mentally disabled children at the Willowbrook State School in Staten Island, New York were intentionally infected with viral hepatitis, in research whose purpose was to help discover a vaccine.[39] From 1963 to 1966, Saul Krugman of New York University promised the parents of mentally disabled children that their children would be enrolled into Willowbrook in exchange for signing a consent form for procedures that he claimed were "vaccinations." In reality, the procedures involved deliberately infecting children with viral hepatitis by feeding them an extract made from the feces of patients infected with the disease.

In 1952, Sloan-Kettering Institute researcher Chester M. Southam injected live cancer cells into prisoners at the Ohio State Prison. Half of the prisoners in this NIH-sponsored study were black. Also at Sloan-Kettering, 300 healthy women were injected with live cancer cells without being told. The doctors stated that they knew at the time that it might cause cancer.

In 1955, the CIA conducted a biological warfare experiment where they released whooping cough bacteria from boats outside of Tampa Bay, Florida, causing a whooping cough epidemic in the city, and killing at least 12 people.

In 1956 and 1957, several U.S. Army biological warfare experiments were conducted on the cities of Savannah, Georgia and Avon Park, Florida. In the experiments, Army bio-warfare researchers released millions of infected mosquitoes on the two towns, in order to see if the insects could potentially spread yellow fever and dengue fever. Hundreds of residents contracted a wide array of illnesses, including fevers, respiratory problems, stillbirths, encephalitis, and typhoid. Army researchers pretended to be public health workers, so that they could photograph and perform medical tests on the victims. Several people died as a result of the experiments.

In 1962, twenty-two elderly patients at the Jewish Chronic Disease Hospital in Brooklyn, New York were injected with live cancer cells by Chester M. Southam, who in 1952 had done the same to prisoners at the Ohio State Prison, in order to "discover the secret of how healthy bodies fight the invasion of malignant cells". The administration of the hospital attempted to cover the study up, but the New York State medical licensing board ultimately placed Southam on probation for one year. Two years later, the American Cancer Society elected him as their Vice President.

In 1966, the U.S. Army released the harmless Bacillus globigii into the tunnels of the New York subway system as part of a field study called A Study of the Vulnerability of Subway Passengers in New York City to Covert Attack with Biological Agents. The Chicago subway system was also subject to a similar experiment by the Army.

Researchers in the United States have performed thousands of human radiation experiments to determine the effects of atomic radiation and radioactive contamination on the human body, generally on people who were poor, sick, or powerless. Most of these tests were performed, funded, or supervised by the United States military, Atomic Energy Commission, or various other US federal government agencies.

The experiments included a wide array of studies, involving things like feeding radioactive food to mentally disabled children or conscientious objectors, inserting radium rods into the noses of schoolchildren, deliberately releasing radioactive chemicals over U.S. and Canadian cities, measuring the health effects of radioactive fallout from nuclear bomb tests, injecting pregnant women and babies with radioactive chemicals, and irradiating the testicles of prison inmates, amongst other things.

Much information about these programs was classified and kept secret. In 1986 the United States House Committee on Energy and Commerce released a report entitled "American nuclear guinea pigs : three decades of radiation experiments on U.S. citizens". In the 1990s Eileen Welsome's reports for The Albuquerque Tribune prompted the Advisory Committee on Human Radiation Experiments, created by executive order of president Bill Clinton. It published results in 1995. Welsome later wrote a book called The Plutonium Files.