To determine if a telephone support behavioral intervention improves depressive symptoms among HIV positive outpatients, we enrolled 177 persons with Beck Depression Inventory (BDI) scores scores of >/=10. Participants were randomized to receive up to 12 scheduled psycho-educational calls over 6 months or to an assessment-only control condition. Co-enrolled informal caregivers of HIV patients received the same telephone intervention in parallel. Among the 160 (90.4%) participants who were re-interviewed at 6 months, 56% were male, and 41% were Caucasian, with a mean baseline BDI score of 22.7. Overall, participants' mean BDI scores improved 5.3 points from baseline, but intervention group differences on depression outcomes including 50% or greater reduction in BDI scores and depression remission were not statistically significant. In the full cohort, men were significantly more likely to improve than women. We conclude that a psycho-educational telephone support intervention did not reduce depressive symptoms for HIV patients more than an assessment-only control condition.