An equally famous or infamous chapter in the history of clinic research is Tuskegee Syphilis Study (1932-1972). It occurred during a research project conducted by the U.S. Public Health Service, where 600 low-income African-American males, 400 of whom were infected with syphilis, were monitored for 40 years.

The participants were given free medical examinations, an incentive to any folks from low-income group; however, they were not told about their disease. Even though a proven cure (penicillin) became available in the 1950s, the study continued until 1972 with participants being denied treatment. In some cases, when subjects were diagnosed as having syphilis by other physicians, researchers intervened to prevent treatment. Many subjects died of syphilis during the study.

The study was stopped in 1973 by the U.S. Department of Health, Education, and Welfare only after its injustice was publicized and it thus became a political embarrassment. In 1974, National Research Act was passed due to the publicity from the Tuskegee Syphilis Study. The Act created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, which was charged to identify the basic ethical principles that should underlie the conduct of biomedical and behavioral research involving human subjects and to develop guidelines which should be followed to assure that such research is conducted in accordance with those principles.

The Tuskegee Syphilis Study is probably the worst case of unethical human subjects research in the history of the United States. In 1997, under mounting pressure, President Clinton apologized to the study subjects and their families.