This study presents the kinetics of CD4/CD25 cell numbers, serum sCD25 levels, and intracellular production and release of interleukin-2 (IL-2) and interleukin-16 (IL-16) in 11 HIV+ patients treated with six cycles of highly active antiretroviral therapy (HAART) plus six MUI of subcutaneous IL-2 compared to 10 HIV+ patients treated with HAART alone. IL-2 therapy induced moderate effects on CD4 T cell recovery and increased CD4/CD25+ cells and sCD25 levels after 2 weeks, while intracellular and secreted IL-2 was reduced and IL-16 was increased at the same time point. After 24 weeks, while HAART-treated patients had increased IL-2 production, in IL-2 treated patients, cytokine production was unaltered compared to pretreatment values. Decreased in vitro IL-2 production may depend on a feedback inhibition by IL-2 infusion. Because of its known antiviral effects, the increased IL-16 production seen after 2 weeks in IL-2-treated individuals may produce beneficial effects on HIV disease. The kinetics of cytokine production may serve to define better the use IL-2 in clinical trials.