To evaluate the sensitivity of treponemal tests as a marker of prior syphilis in individuals with human immunodeficiency virus (HIV) infection, the syphilis serology of 109 homosexual men with a documented history of treated syphilis was compared with records of prior results and confirmed on stored serum samples. None of the HIV-seronegative individuals lost reactivity to a treponemal test, whereas 7% of the seropositive asymptomatic individuals and 38% of those with symptomatic HIV infection had loss of reactivity. Symptomatic HIV infection was associated with loss of reactivity, as a T4 lymphocyte count less than 200 X 10(6)/1, a T4-to-T8 ratio less than 0.6, a single prior episode of syphilis, and a low VDRL titer at the time of the last documented episode of syphilis. Although no conclusions can be drawn about the sensitivity of treponemal tests in patients with active syphilis and HIV infection, these data suggest that treponemal tests may not identify those previously infected with Treponema pallidum.