OBJECTIVE: To recommend a cost-effective approach for the management of acute male urethritis in the developing world, based on the findings of a theoretical study. METHODS: A model was developed to assess the cost-effectiveness of three urethritis management strategies in a theoretical cohort of 1000 men with urethral syndrome. (1) All patients were treated with cefixime and doxycycline for gonococcal urethritis (GU) and nongonococcal urethritis (NGU), respectively, as recommended by WHO. (2) All patients were treated with doxycycline for NGU; treatment with cefixime was based on the result of direct microscopy of a urethral smear. (3) All patients were treated with cotrimoxazole or kanamycin for GU and doxycycline for NGU. Cefixime was kept for patients not responding to the first GU treatment. Strategy costs included consultations, laboratory diagnosis (where applicable) and drugs. The outcome was the rate of patients cured of urethritis. Cost-effectiveness was measured in terms of cost per cured urethritis. RESULTS: Strategy costs in our model depended largely on drug costs. The first strategy was confirmed as the most effective but also the most expensive approach. Cefixime should cost no more than US$ 1.5 for the strategy to be the most cost-effective. The second strategy saved money and drugs but proved a valuable alternative only when laboratory performance was optimal. The third strategy with cotrimoxazole was the least expensive but a low follow-up visit rate, poor treatment compliance or lower drug efficacy limited effectiveness. Maximizing compliance by replacing cotrimoxazole with single-dose kanamycin had the single greatest impact on the effectiveness of the third strategy. CONCLUSION: Our model suggested that a cost-effective approach would be to treat gonorrhoea with a single-dose antibiotic selected from locally available products that cost no more than US$ 1.5.