The control of sexually transmitted diseases, including HIV-1, among sex workers and their clients in urban areas in developing countries, is considered a valuable and cost-effective intervention to contain the spread of HIV-1. The effect of a programme of STD treatment combined with condom promotion on HIV-1 incidence has so far not been measured. During an intervention including condom promotion, as well as monthly sexually transmitted disease screening and treatment among 531 initially HIV-1 negative female sex workers in Kinshasa, Zaire, 70 became infected with HIV-1 (incidence of 8.0 per 100 women-years [wy]). A decline of HIV-1 incidence was observed over time, from 11.7/100 wy during the first 6 months, to 4.4/100 wy over the last 6 months, 3 years later (p = 0.003). Simultaneously, regular use of condoms with clients went up from 11% to 52% and 68%, after 6 and 36 months of intervention, respectively. Risk factors for HIV-1 seroconversion after multivariate analysis included irregular condom use (RR 1.6 [95% Cl 1.1-2.8]), gonorrhoea (RR 2.5 [1.1-6.4]), trichomoniasis (RR 1.7 [1.1-2.8]), and genital ulcer disease (RR 2.5 [1.1-6.4]), during the probable period of acquisition of HIV-1. In women who attended more than 90% of their clinic appointments, the HIV-1 incidence was 2.7/100 wy compared to 7.1, 20.3, and 44.1 per 100 wy among women who attended 76-90%, 50-75%, and less than 50% of the monthly appointments, respectively (p < 0.0001). These trends remained after controlling for reported condom use and number of clients. This study confirms earlier findings that STDs facilitate transmission of HIV-1 and shows that a clinic-based intervention consisting of STD care and condom promotion can result in a major decline of HIV-1 incidence among female sex workers.