To examine the extent of infection with syphilis in an inner-city community, we determined the prevalence, incidence, and correlates of syphilis seroreactivity in a representative sample of unmarried whites, African Americans, and Hispanics living in San Francisco during 1988 to 1989 and again 1 year later in 1989 to 1990. One thousand seven hundred seventy single men and women aged 20 to 44 were surveyed in a random household sample drawn from three neighborhoods of varying geographic and cultural characteristics. Syphilitic infection was determined by testing specimens with the microhemagglutination assay for antibodies to Treponema pallidum (MHA-TP). Of blood samples available from 1262 participants from the initial survey, 32 (2.5%) were MHA-TP reactive. After adjustment for age, a reactive syphilis serology was significantly predicted (P < 0.05) by African American race, homosexual activity (men), and less education. In homosexually active men, lifetime number of male sex partners and the presence of antibody to the human immunodeficiency virus (HIV) significantly predicted syphilis seroreactivity (P < 0.01). One year later, of 841 specimens available for testing, an additional 13 (1.5%) had become MHA-TP reactive. Eleven (85%) of the new cases were in heterosexual men and women. Although San Francisco citywide incidence data indicate that syphilis may be decreasing for the city as a whole, incidence data on a community level suggests that syphilitic infection is increasing in high-risk heterosexual communities. Thus, syphilis prevention programs should rely on serologic testing at the community level to plan effective intervention strategies.