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Lymphoid tissues from asymptomatic HIV-infected individuals, as compared with symptomatic HIV-infected subjects, show limited histopathological changes and lower levels of HIV expression. In this report we correlate the control of HIV replication in lymph nodes to the non-cytolytic anti-HIV activity of lymphoid tissue CD8⁺ cells. Five subjects at different stages of HIV-related disease were studied and the ability of their CD8⁺ cells, isolated from both lymphoid tissue and peripheral blood, to inhibit HIV replication was compared. CD8⁺ cells from lymphoid tissue and peripheral blood of two HIV-infected long-term survivors suppressed HIV replication at a low CD8⁺:CD4⁺ cell ratio of 0.1. The CD8⁺ cells from the lymphoid tissue of a third asymptomatic subject suppressed HIV replication at a CD8⁺:CD4⁺ cell ratio of 0.25; the subject’s peripheral blood CD8⁺ cells showed this antiviral response at a lower ratio of …