Initiation of antiretroviral monotherapy early in the course of infection with human immunodeficiency virus may result in a temporary slowing in the rate of disease progression; however, little is known about the virologic effects of early therapy. Virus load was measured in peripheral blood and lymph nodes from 16 antiretroviral-naive patients with a mean CD4 T lymphocyte count of 659 cells/microliter at baseline and after 8 weeks of either no treatment or zidovudine therapy. CD4 T lymphocyte counts and all virologic parameters examined remained unchanged regardless of zidovudine treatment status. Histopathology and virus distribution within lymph nodes remained constant between baseline and week 8 in each patient, indicating that the virologic and histologic parameters examined in a single lymph node are representative of a systemic process. Early antiretroviral monotherapy with zidovudine had no effect on virologic parameters in this group of patients with relatively high CD4 T lymphocyte counts and low measures of virus load at baseline.