T he extent of antiviral activity exhibited in vitro by CD8+lymphocytes from individuals infected by HIV-1 correlates significantly with their clinical status. CD8+ lymphocytes from asymptomatic subjects were found to inhibit HIV-1 replication by 90% or greater at effector/target (E/T) ratios ranging from as low as 0.05 to 0.25. CD8+ cells from 17 of 19 (89%) of these subjects suppressed replication at an E/T ratio of 0.10 or less. CD8+ lymphocytes from symptomatic patients (non-AIDS) inhibited HIV-1 replication at E/T ratios ranging from 0.05 to 1.0, and CD8+ cells from 8 of 13 (62%) required ratios greater than 0.10. As a group, patients with AIDS exhibited the lowest degree of anti-HIV activity with their CD8+ lymphocytes. The effective range of E/T ratios from AIDS patients was 0.10-2.0, and 9 of 10 (90%) required E/T ratios greater than 0.25. This anti-HIV activity exhibited by CD8+ cells also correlated significantly with the subject's peripheral blood CD4+ cell count. The relative extent of CD8+ cell anti-HIV-1 activity was not found dependent on variations in the CD4+ target cells and viruses used. These findings suggest that the decreased CD8+ cell antiviral activity is related to progression to disease in HIV-infected individuals.