The Tuskegee syphilis study of "untreated syphilis in the male Negro" became the longest-running nontherapeutic and racist research study in American history. Approximately 399 African-American men with syphilis and 201 without the disease who served as controls were followed, but deliberately not treated for their illness, in several counties surrounding Tuskegee, Alabama, between 1932 and 1972. The men, however, did not know they were participating in a study being run by the United States Public Health Service (PHS). They were told they were being treated for "bad blood," a local term used to cover venereal diseases, as well as anemia and other ailments.

In 1932, syphilis was only one of many problems that plagued the black population in Tuskegee and the surrounding Macon County. "Cash money" was often hard to come by, and many families were sharecroppers who were in perpetual debt. One survivor of the Tuskegee study who lived about twenty miles outside of town recalled, for example, that during the 1930s he could not drive his car because he did not have cash to pay for licensing tags.

In the heart of Alabama's "black belt," serious malnutrition, inadequate housing, illness, and illiteracy were widespread, especially as the Depression deepened. Illnesses were borne or cured with the help of local folk healers. People occasionally sought treatment from doctors, but physician visits to rural homes were uncommon and expensive. In a 1932 survey of 612 black families, only 258 of the families had seen a physician during the year. Despite the existence of both a black-run U.S. Veteran's Administration hospital and the John A. Andrew Hospital at Tuskegee Institute, the historically black college founded by Booker T. Washington, it was difficult for people living in the country to come to town or pay for clinic visits.

The syphilis study started as part of the Rosenwald Foundation's work to improve educational and health conditions for black southerners. The foundation, in conjunction with the PHS, began a survey and treatment program on syphilis in six southern counties in 1929. The highest rates of syphilis were found in Macon County, where few people had been treated.

When the funds for the surveys and treatment program ran out, several of the PHS researchers realized that the area around Macon County would serve as a "perfect" laboratory to study untreated syphilis. In 1932 there were medicines available, but they required a long period of treatment. Medical wisdom at the time also assumed that patients who had survived to the disease's latent or tertiary stage probably could not be helped by the then known treatments. It was also thought that African Americans were more prone to cardiovascular complications from the disease and that whites were more likely to develop neurological symptoms. The researchers hoped to show whether racial differences existed.

The study of untreated syphilis began in 1932. It was only supposed to last six to twelve months. Physicians and nurses from the PHS, the local health department, and Tuskegee Institute selected and followed the men. They were given aspirin, iron pills, and tonics, and were told that they were being treated. Spinal taps were ordered to monitor the progress of their disease; the men were told these were "back shots." Autopsies were needed to examine syphilis's effect on the body more definitively. In order to obtain permission for autopsy the families were promised money for burials. In 1936, the first of what would become the pattern for twelve other reports on the study was published in a respected and widely read medical journal. The findings made clear that the lack of treatment had shortened many of the men's lives.

As the study progressed during the 1940s, penicillin became recognized as a certain cure for syphilis, although it would probably not have helped the men with advanced cases of the disease. The study continued throughout the 1960s, through the civil rights era, and even after more formal ethical canons were promulgated that would have made such a study unthinkable.

In 1972 a horrified investigator revealed the story of the Tuskegee syphilis study to a reporter. When newspapers reported the story, a huge public outcry erupted, followed by congressional hearings, a federal investigation, and a lawsuit that provided some compensation to the men and their families. No one was ever prosecuted for their role in the study. In 1997, President Bill Clinton apologized to the six remaining survivors, their families, and the entire African-American community. The Tuskegee syphilis study remains a monument to racialized assumptions about disease and to unethical behavior in research.