Somatic symptoms often complicate the diagnosis and psychopharmacological treatment of depression in HIV illness. We treated 33 depressed HIV-positive men and women with medically symptomatic HIV or AIDS (CDC stages 2B, 2C, 3B, or 3C) in a 6 week open-label trial with sertraline, paroxetine, or fluoxetine, to assess their effectiveness and tolerability. We further assessed whether treatment of depression resulted in a reduction in both affective and somatic symptoms in this medically ill population. Twenty-four subjects (73%) completed the trial (7 on sertraline, 7 on paroxetine, 10 on fluoxetine), 20 (83%) of whom were clinical responders. Nine dropped out within 1-3 weeks of treatment because of adverse effects, mostly agitation, anxiety, and insomnia. Subjects who completed 6 weeks of SSRI treatment experienced significant reductions in both affective and somatic symptoms, many of the latter having been attributed to HIV rather than depression. These results suggest that, even in later stages of HIV illness, the contribution of depression to perceived somatic symptoms may be significant, and that these symptoms may improve with antidepressant treatment.