In 1990, 20 asymptomatic persons diagnosed with the human immunodeficiency virus (HIV-positive) and mild-to-moderate depression were divided into 2 comparison groups. One group received structured group therapy plus fluoxetine, while the other received the same therapy plus a placebo. Affective, neurocognitive, and immune variables were measured before and after the intervention. In the patients receiving group therapy and fluoxetine, its administration did not improve treatment outcome compared to the therapy and placebo group. No significant differences between the two groups were noted on immune variables. However, symptoms of depression decreased in both groups, and both groups showed significant incorporation of the skills in active behavioral coping taught in therapy.