In 1932, the U.S. Public Health Service began a study of untreated syphilis among black men in Macon County, Alabama. This project, later known as the Tuskegee Syphilis Study, became one of the most notorious ventures of twentieth-century medicine. Much has been written on it. Historians have suggested that scientific racism strongly influenced the study. But specific links between earlier racial science and the scientific conduct of the study have remained unexplored. The examination in this paper of the concept of a racially determined resistance to syphilis in the nervous system establishes such a link. Discussion of nervous resistance to syphilis appeared in the medical literature in the early twentieth century as a conjecture about the natural inferiority of blacks. White physicians used the concept to interpret racial differences in neurosyphilis as evidence of the rudimentary development of the brain. A small community of African American physicians joined other national experts in syphilis who chose to explain apparent racial differences through alternate mechanisms. But the scientific advisors to the Tuskegee Syphilis Study favored the concept of a racial resistance to neurosyphilis and steered the early design of the study to help to elucidate it. The Tuskegee Syphilis Study was an examination of untreated syphilis, but it also became a demonstration of a putative racial characteristic of syphilis long considered evidence of the natural inferiority of blacks. An examination of the concept of racial nervous resistance and its influence on the research in Macon County helps to define the influence of scientific racism on this notorious medical study.