The objective was to measure the gender-specific differences for syphilis and for the sexual transmission of human immunodeficiency virus (HIV) in a cross-sectional analysis of injecting drug users (IDUs) admitted to detoxification between February 1987 and January 1990. HIV was determined by enzyme-linked immunosorbent assay (ELISA) and confirmed with Western blot. For syphilis reactive samples to a rapid plasma reagent (RPR) were confirmed with treponemal tests (FTA-ABS or MHA-TP). Of the 386 heterosexual IDUs, 68% were HIV-positive and 4.7% had serologic syphilis (RPR and FTA-ABS or MHA-TP positive). Syphilis was higher in women (12%) than in men (3%), and women reported a significantly (P < 0.001) higher number of sex partners. Men had an IDU as a sex partner more often than women did (P = 0.001). Serologic syphilis in women was associated with having had more than one sexual partner in the previous year (P = 0.028) but this association was not present in men. HIV infection was not associated with syphilis in male IDUs. However, HIV was present in all women with syphilis that reported more than one partner.