Recent studies in the literature point out that HIV-infected subjects are affected by depression with a relatively high frequency. The aim of this study was to assess the efficacy and tolerability of paroxetine for the treatment of depression in the context of HIV infection. 15 HIV-infected subjects (10 patients with a major depressive episode and 5 patients with an adjustment disorder with depressed mood, according to the DSM IV diagnostic criteria) were administered paroxetine at a daily dosage of 20 mg. Depressive symptomatology was monitored by means of the Hamilton Rating Scale for Depression (HAM-D) at the time of enrollment and 2 weeks, 4 weeks, and 6 weeks later; at the same times adverse effects were recorded. 14 patients completed the study, and all of these recovered from depression; HAM-D mean scores significantly improved from baseline to final assessment, both when all subjects were considered (ANOVA for repeated measurements: p < or = 0.0001) and when only patients with a major depressive episode were included in the statistical analysis (ANOVA for repeated measurements: p < 0.0001). No significant adverse effects were recorded. Because of its efficacy and good tolerability paroxetine seems to be suitable for the treatment of depression in the context of HIV infection.