The effect of zidovudine therapy on human immunodeficiency virus (HIV)-specific antibody production was studied in 64 HIV-1-infected infants and children > 6 months old. HIV-specific in vitro antibody production (IVAP) was measured in cultures of peripheral blood mononuclear cells (PBMC). IVAP decreased in 85% of children after zidovudine was initiated (mean decline, 1 log within 2 months). Effects were seen as early as 1 week after starting zidovudine. No change in IVAP was seen in children not treated. In comparison, plasma core (p24) antigen levels declined and CD4+ lymphocytes increased in only 42% and 52%, respectively, of treated subjects. Thus, the production of antibody to HIV-1 decreases rapidly after the initiation of antiretroviral therapy. This response to therapy may provide a simple and sensitive method of monitoring antiretroviral therapy.