UNETHICAL USES OF HUMANS AS RESEARCH SUBJECTS represent appalling chapters in the history of medicine. To ensure that effective protections against such abuses continue to evolve and improve, it is essential to continue to learn from historical examples. Sadly, a new example has recently come to light. While conducting research on the Tuskegee study of untreated syphilis, Wellesley College Professor Susan Reverby recently reviewed the archived papers of John Cutler, a US Public Health Service (PHS) medical officer and a Tuskegee investigator. Instead of finding Tuskegee records, however, Reverby found the records of another unethical study. In this study, vulnerable populations in Guatemala—mentally incapacitated patients, prison inmates, sex workers, and soldiers— were intentionally exposed to sexually transmitted infections (syphilis, gonorrhea, and chancroid). The work was directed by Cutler and was done with the knowledge of his superiors, including then Surgeon General Thomas Parran Jr. Funded with a grant from the National Institute of Health (NIH) to the Pan American Sanitary Bureau (which became the executive arm of the Pan American Health Organization), the study was conducted in cooperation with Guatemalan investigators by the USPHS Venereal Disease Research Laboratory, which 10 years later became a part of the Centers for Disease Control and Prevention (CDC). As described by Reverby, the study’s initial syphilis experiments used female sex workers, intentionally infected with Treponema pallidum, as a source of infection to male prison inmates. At that time, sex workers were allowed into Guatemalan prisons. When the rates of female-to-male transmission proved to be low, the research approach changed to the direct inoculation of prison inmates and patients in the Guatemalan mental hospital. Most inoculation experiments involved subcutaneous injection of T pallidum or exposure of the penile foreskin to infectious material. The majority of study subjects were treated with penicillin, although available study records do not document therapy or completion of therapy for all subjects and some received only partial treatment. One study subject, a patient with a history of severe epilepsy, died of status epilepticus during treatment with penicillin. Although additional deaths occurred during the conduct of the study in the mental hospital, they were most likely related to the high rates of underlying disease, such as tuberculosis. The investigators provided some items for institutional support, such as anticonvulsant medications and refrigerators to store vaccines, and offered cigarettes as an incentive to study subjects. The archives provide no indication that individuals understood that they were participating in research. Most of the gonorrhea and chancroid experiments were conducted with Guatemalan soldiers. While the initial studies involved sexual contact of soldiers with female sex workers who had been infected with gonorrhea, subsequent subjects were infected through intraurethral inoculations of Neisseria gonorrhoeae and cutaneous inoculations of Haemophilus ducreyi, and then treated with penicillin and sulfathiazole, respectively.