In this article, the author seeks to analyze the endemic character of syphilis and its repercussions on the residents of Mexico City, particularly in the 19th Century. The article reviews the etiology of syphilis, its clinical diagnosis, modes of infection and prevention measures, as well as the controversy surrounding the smallpox vaccine and inoculation against syphilis. Questions surrounding its presence among various social groups, divided by sex and age, are examined through the use of two types of primary sources. The first consists of historical documents: lists of patients registered at hospitals and of the deceased, including information on their place of origin, age, sex and cause of death, as well as contemporary medical studies such as dissertations, treatises and publications on diagnostics, prophylaxis, prevention, modes of infection and experiments aimed at the creation of a vaccine. The second source consists of data obtained from the skeletons of hundreds of Mexico City residents with traces of syphilis, which provide irrefutable proof of the disease's dissemination throughout all sectors of society. The skeletons have been obtained from 17th Century to 19th Century cemeteries, churches and hospitals. The secondary sources include research on hospitals, public health and prostitution, which are central concerns. Sanitary control and its relationship to prostitution in this epoch is also relevant, as one of the skeletons was obtained from San Juan de Dios, a hospital that cared for prostitutes and patients with syphilis in the second half of the 19th Century.