We evaluated the role of CD34+ bone marrow progenitor cells in vivo, in the pathogenesis of AIDS-related haematological abnormalities. The clonogenic activity of CD34+ cells from seven patients with HIV-1 infection, without bone marrow involving opportunistic infections or neoplasms, was assessed in semisolid cultures. The number of CFU-GM was significantly reduced as compared to the controls (P = 0.017), independently from myelotoxic therapy, while the number of BFU-E was not. The presence of retroviral sequences in CFU-GM colonies from four patients and in the total population of CD34+ cells from six patients with advanced stage HIV infection was investigated using the polymerase chain reaction. The presence of HIV-1 sequences was also searched for in a purified suspension of CD34+ cells after 3 weeks liquid culture. All these cells were always HIV-1 negative, while viral sequences were always detected in bone marrow mononuclear cells from these and other patients. The number of HIV-1 DNA copies decreased with increasing enrichment. At most 1:10,000 CD34+ cells are infected in vivo. Other mechanisms than direct viral infection of progenitor cells must account for the defective haemopoiesis in HIV-1 infected patients.