Patients with acquired immunodeficiency syndrome (AIDS)-related complex and asymptomatic individuals seropositive for human immunodeficiency virus (HIV) have depressed natural killer (NK) activity. Normal human macrophages cultured for 3-7 days significantly up-regulated the NK activity of mononuclear cells obtained from the blood of asymptomatic HIV-seropositive individuals and patients with AIDS. Following a 4-hr incubation of patients' cells with in vitro-differentiated macrophages, the greatest augmentation of NK activity was seen in asymptomatic HIV-seropositive individuals who were receiving treatment with azidothymidine. Stimulation of macrophage immunoregulatory activities or adoptive immunotherapy with ex vivo-activated monocytes may be beneficial in HIV-infected patients.