Human immunodeficiency virus (HIV) infection often has effects on the hematopoietic system which can be distinguished from the concurrent effects of medications or opportunistic infections. Exactly how the virus mediates these effects remains uncertain, but both in vivo and in vitro studies have pointed up possible direct and indirect modes of hematopoietic suppression. Whether a significant fraction of CD34+ cells in vivo are infected with HIV remains controversial, but most studies using in situ polymerase chain reaction techniques would suggest not. Other more indirect modes of hematopoietic cell suppression such as production of autoantibodies, production of other humoral inhibitory factors, T-cell mediated suppression of hematopoiesis, or production of inhibitory or stimulatory cytokines may also be contributory. It is probable that several of these mechanisms may occur simultaneously, and an increased understanding of their role may lead to improved strategies to correct the cytopenias which often accompany HIV disease.