OBJECTIVE: The authors present preliminary data from two treatment modalities of a randomized clinical trial in which they compared 16- week interventions of interpersonal psychotherapy to supportive psychotherapy. METHOD: HIV-positive patients who were not acutely medically ill and had scores of 15 or higher on the Hamilton Depression Rating Scale were randomly assigned to one of four treatment modalities. They were assessed by the Hamilton scale and Beck Depression Inventory at 8 and 16 weeks. Most subjects who underwent either interpersonal psychotherapy (N = 16) or supportive psychotherapy (N = 16) were male, gay or bisexual, white, and college educated. RESULTS: Results of last-observation-carried-forward and completer analyses showed that scores on the Hamilton scale and Beck Depression Inventory decreased significantly for both treatments. Differential improvement for interpersonal psychotherapy appeared by midtreatment (week 8) and persisted at termination. CONCLUSIONS: This is the first controlled study of individual psychotherapies for depressed HIV- positive patients. Results suggest that a specific antidepressant psychotherapy, interpersonal psychotherapy, has advantages over a supportive therapy.Abstract Teaser