Interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) are not constitutively produced by human mononuclear phagocytes. In the present study we have investigated the production of these cytokines in human blood-derived macrophages (BDM) after infection with 16 primary HIV-1 blood isolates obtained from individuals at different stages of disease. In addition, we monitored the replicative capacity of these primary isolates in blood-derived macrophages over a 3-month period. Production of IL-1 alpha was detected in two cultures, IL-beta was positive in two other cultures, and both IL-1 alpha and IL-beta were present in three additional macrophage cultures. IL-1 alpha production was also detected in BDMs infected with the laboratory strain HIV-1 IIIB. In contrast, TNF-alpha was not found in any of the culture supernatants tested. All primary HIV-1 isolates used in these experiments were able to infect BDM productively irrespective of the clinical stage of the patients at the time of virus isolation. The production of IL-1 was mostly found in chronically infected cultures displaying low levels of HIV-1 replication. These results indicate that macrophages tropism is a general feature of all HIV-1 isolates. Furthermore, release of IL-1 by mononuclear phagocytes upon HIV-1 infection may contribute to the pathogenesis of HIV-1 related diseases.