In vitro survival of monocytes (MO) was studied in 59 patients with HIV infection of different clinical stages. MO from 61 donors and 12 healthy seronegative homosexual men were also examined. Compared with the number of MO seeded, the percentage of adherent monocyte-derived macrophages (MDM) present after 10 days was significantly lower in patients with HIV infection than in the controls. However, the number of viable, non-adherent MO/MDM was similar in patients and controls. Our data indicate markedly decreased in vitro survival of MO from patients with HIV infection. After 10 days, the MDM population in the patient cultures was significantly less differentiated than the control cells, assessed by immunocytochemical staining with monoclonal antibodies against differentiation antigens. Reduced in vitro survival of MO/MDM was associated with low numbers of CD4+ and CD8+ lymphocytes in blood, reduced lymphocyte mitogen responses, presence of HIV p24 antigen in serum and advanced clinical stage. Decreased in vitro survival of MO/MDM may be associated with HIV replication in the cells. Although the level of HIV replication in the cultures was low as assessed by measurement of HIV p24 antigen in culture supernatants and staining of MO/MDM for HIV antigens, cytopathogenic effects of HIV or HIV products cannot be ruled out.