Factors contributing to the development of cytopenias in patients with advanced human immunodeficiency virus (HIV) disease include primary HIV-related suppression of blood cell production, opportunistic infections and neoplasms that directly involve the marrow cavity, and the toxicity of antiviral, antiinfective, and antineoplastic therapy. Indeed, bone marrow toxicity is often the complication limiting delivery of effective therapy in such patients. Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to increase the leukocyte count in this patient population. Although there is concern that GM-CSF administration may increase HIV replication in myeloid cells, this effect has not been observed in clinical studies. In addition, the most appropriate use of hematopoietic growth factors would be in combination with effective antiretroviral agents, such as zidovudine. A pharmacologic basis for such combination is provided by the finding that inhibition of HIV by zidovudine may be augmented by GM-CSF. It recently has been shown that patients with severe leukopenia and intolerance to zidovudine can have reconstitution of effective myelopoiesis with low doses of subcutaneously self-administered GM-CSF and become hematologically tolerant of zidovudine 1,200 mg/d. The major adverse effects of this combination regimen were constitutional symptoms and thrombocytopenia. Further investigation of GM-CSF and other hematopoietic growth factors in this patient population is warranted.