OBJECTIVES: To determine age-sex specific seroprevalence and incidence rates of Treponema pallidum, Haemophilus ducreyi, and HSV-2; to assess the association between HIV-1 status and incidence of these STIs; and HSV-2 serostatus with number of lifetime sexual partners. METHODS: Antibodies against HIV-1, T pallidum, H ducreyi, and HSV-2 infections were tested using approximately 1000 paired (2 year interval) sera collected from a rural adult (15-54 years) population cohort in south west Uganda. RESULTS: Overall HIV-1 prevalence was 4.9%. Prevalence for T pallidum was 12.9% among males and 12.6% among females. The corresponding rates for H ducreyi were 9.8% and 7.3% respectively. HSV-2 prevalence rates were considerably lower in males (36.0%) than in females (71.5%), p < 0.001. Incidence rates for T pallidum per 1000 person years of observation were 8.4 for males and 12.3 for females. The corresponding rates for H ducreyi were 24.6 and 20.0 and for HSV-2 were 73.2 and 122.9 per 1000 person years of observation, respectively. The RR of HSV-2 incidence was 3.69 in HIV seropositive cases versus HIV seronegative after adjusting for age and sex. The corresponding RR for H ducreyi was 3.50 among female HIV positive cases versus negatives with no effect seen in males. Association between HIV-1 prevalence and prevalence of other STIs was significant (Mantel-Haenszel test) for H ducreyi (p = 0.01) and for HSV-2 (p = 0.004) but not for T pallidum (p > 0.4). HSV-2 prevalence was associated with number of lifetime sexual partners (females, p = 0.003; males, p = 0.08). CONCLUSIONS: The results have provided a reliable estimate of the magnitude of the STI problem and demonstrated an association between HIV-1 status and serology of other STIs in a general rural population in sub-Saharan Africa. The study has also highlighted a correlation between HSV-2 seropositivity and number of reported lifetime sexual partners.