BACKGROUND: Pharmacological treatment of depression in HIV-infected patients has been found to be effective. This study assessed the efficacy and feasibility of treatment with fluoxetine and the best method of administering the drug to patients with HIV infection. METHODS: Sixteen seropositive and 16 seronegative patients, equally matched for age and sex, who had Hamilton Rating Scale for Depression scores of at least 16 and who received at least 20 mg/d of fluoxetine for 8 weeks were studied. RESULTS: Depression was alleviated in both groups. However, improvement in the seropositive patients occurred later. INTERPRETATION: The results confirm the effectiveness of fluoxetine in treating depression in people with HIV infection. The lack of adverse effects makes this treatment particularly suitable, especially because seronegative people take longer to respond to treatment.