The amount of human immunodeficiency virus type 1 (HIV-1) in various tissues was investigated by polymerase chain reaction (PCR) in 16 patients with end-stage HIV-1 infection and 7 patients with symptomatic but less advanced disease. During postmortem study of the 16 end-stage patients, HIV-1 DNA was found most often in lymph nodes and the spleen (both 100%), lung (93.8%), and colon (87.5%). Biopsied lymph nodes from the 7 symptomatic patients contained substantially higher copy numbers of HIV-1 RNA and DNA than did peripheral blood mononuclear cells (PBMC). Plasma viral RNA levels correlated significantly with the amount of HIV-1 RNA in PBMC (r2 = .86, P = .0025) but not with the level of viral RNA in lymph nodes in patients with symptomatic HIV-1 infection. These data suggest that although lymph nodes represent the main site for HIV-1 infection and replication, the level of circulating viral burden may not be solely determined by the magnitude of active HIV-1 replication in lymph nodes.