OBJECTIVE: Among persons with sexually-transmitted diseases (STD), the proportion that is also infected with HIV is higher than in the general population. Since many cases of HIV infection remain undetected during the asymptomatic stage, HIV-infected patients are likely to perform the same sexual behavior as before and put partners at risk of infection. Detection of asymptomatic HIV infection will enable the person to protect partners by changing sexual behavior, reducing the number of secondary transmissions. Therefore, HIV screening in clinics for sexually transmitted diseases (STD-clinic) is a potential tool to control the epidemic. In our analysis we estimate the cost-effectiveness of universal HIV screening of patients attending a STD-clinic in Amsterdam. METHODS: Cost-effectiveness analysis. A Bernoulli model for the secondary transmission of HIV was linked with epidemiological data on infection with HIV and other STD in patients attending a STD-clinic in Amsterdam from 1991 to 1997. This gave estimates of the number of secondary HIV infections caused by visitors to the STD-clinic. Combined with data on the health and monetary benefits of averting HIV-infection and costs of HIV-screening, we assessed the cost-effectiveness of HIV-screening of visitors to the STD-clinic. Standard techniques for cost-effectiveness analysis were used, and both costs and life years gained were discounted at 4%. RESULTS: Increased risk for HIV infection was found in STD clinic attenders infected with another STD. (Odds ratio: 2.07) The risk differed for different STDs, with the highest odds ratios for syphilis and gonorrhoea. Screening of all attenders was estimated at a net costs of € 82,552 per secondary infection averted, with a cost-effectiveness ratio of € 1637 per life year gained (LYG). The cost-effectiveness ratio ranges between € 680 and € 9335 per LYG, depending on key parameters in the model. CONCLUSION: Compared to other interventions in infectious disease control in the Netherlands, this intervention has an acceptable cost-effectiveness.