Interleukin-2 (IL-2) is a key cytokine in cellular immunity. Human immunodeficiency virus type 1 (HIV-1)-infected individuals lack IL-2 because of low CD4+ T lymphocyte numbers. In an attempt to enhance cellular immunity, low-dose recombinant human (rh) IL-2 at 10 micrograms or 180,000 units or its polyethylene glycol (PEG) derivative at 9 micrograms or 36,000 units was given by intracutaneous injection to 8 HIV-1-infected men for 30 days. Participants had no evidence of opportunistic infection and received concurrent zidovudine. IL-2 treatment was nontoxic and elicited a local cellular response resembling classic delayed-type hypersensitivity (DTH) with local interferon-gamma production, even in anergic patients. Systemic responses included enhanced DTH responses to recall antigens, improved in vitro proliferative responses to mitogen, and enhanced NK cell activity. Peripheral leukocyte phenotype and virus titers were unchanged. Long-term studies of low-dose IL-2 are warranted to determine whether immunoenhancing effects can be sustained and if they are associated with improved clinical course.