In order to assess the efficacy and safety of recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) in the treatment of HIV-associated leukopenia, 35 subjects suffering from severe leukopenia/neutropenia (24 with a previous diagnosis of AIDS, 11 with AIDS-related complex), received rHuGM-CSF at 0.5-3 micrograms/Kg/day subcutaneously for a mean period of 9.7 +/- 12.5 weeks (range 2-43 weeks). Five patients have been treated continuously for more than 6 months. rHuGM-CSF administration led to a significant (at least two-fold; P < .001) increase in total leukocyte, neutrophil and monocyte count by the second week of treatment, subsequently maintained through the entire course of therapy. No considerable effects on other hematological, immunological and virological parameters have been detected. Patients treated with rHuGM-CSF did not suffer from novel opportunistic diseases, while bacterial infections occurred in only 3 cases (pneumonia in 2, otitis/mastoiditis in 1). Long-term treatment with rHuGM-CSF allowed continuation or resumption of potentially myelotoxic drugs in 22 patients out of 35. A self-limited flu-like syndrome represented the most common adverse event (observed in 15 patients), while no other significant clinical or laboratory abnormalities were found. In conclusion, long-term rHuGM-CSF therapy showed a good efficacy and safety profile in the treatment of HIV-related leukopenia, also increasing tolerability to potentially myelosuppressive drugs, and leading to a significant reduction in morbidity due to secondary infections.