A serologic survey of 4863 patients attending two inner-city sexually transmitted disease clinics was conducted in 1988 1 year after an initial survey to reassess the prevalence and associated risk factors for human immunodeficiency virus (HIV) infection. The HIV seroprevalence rates had not changed significantly (5.2% in 1987, 4.9% in 1988), and remained higher among men (5.6%) than among women (3.6%). The HIV seroprevalence increased steadily with age, to 34 years in women and to 39 years in men. Of patients with a reactive syphilis serologic test result, 24.3% were HIV infected compared with 3.5% of patients with a nonreactive test for syphilis. In multivariate analysis, a reactive serologic test for syphilis was significantly associated with HIV infection in all major risk behavior categories. Among heterosexuals who denied parenteral drug abuse, HIV infection rates were 6.8 and 8.7 times greater for women and men, respectively, who had a reactive serologic test for syphilis. Evidence of heterosexual transmission of HIV was further suggested by a change in HIV seroprevalence in women from 3.0% in 1987 to 3.6% in 1988, a male to female HIV infection ratio of 1.6, and a 3.0% prevalence of infection among patients who denied established risk factors. This was most evident among those younger than 25 years, in whom 72% of infected women and 46.2% of infected men denied high-risk behaviors. These data demonstrate the strong association between syphilis and HIV infection and the importance of heterosexual HIV transmission in patients attending sexually transmitted disease clinics. This study underscores the need for a more comprehensive control program for sexually transmitted diseases, including syphilis and HIV infection.