Peripheral blood mononuclear cells from 12 asymptomatic patients infected with immunodeficiency virus (HIV) and 4 patients with AIDS were analyzed before and during therapy with zidovudine for T helper cell (Th) function. Th function improved by more than fourfold to one or more of three stimuli tested in 9 (75%) of 12 asymptomatic patients on zidovudine therapy and in 3 of 4 patients with AIDS. Only 6 (7.4%) of 80 untreated HIV-infected control patients showed spontaneous improvement in Th function (P less than 10(-6)). Improved Th function was detected as early as 5 weeks into therapy in 6 patients and continued to be evident for greater than 1 year after start of therapy in 6 patients and for greater than 2 years in 2 patients. No correlation was observed between improved Th function and changes in CD4+ or CD8+ cell numbers or in levels of serum HIV p24 antigen or beta 2-microglobulin. These results suggest inclusion of in vitro Th function as a useful marker in determining the efficacy of antiretroviral drug therapy of HIV-infected patients.