Study Objective: To define the clinical and hematologic effects of subcutaneously administered bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Design: Single arm nonrandomized dose escalation study. Patients: Twenty-one patients with advanced malignancy who were not receiving concurrent myelosuppressive therapy. Interventions: Subcutaneous administration of rhGM-CSF by one-daily injection to groups of two to four patients at doses of 0.3 to 30 μg/kg body weight · d for 10 consecutive days. Some patients received a second 10-day period of daily rhGM-CSF treatment after a 10-day nontreatment interval followed by alternate-day treatment. Clinical status and hematologic values were monitored frequently. Measurements and Main Results: All doses of rhGM-SCF caused an immediate transient fall of 84% to 99% in circulating neutrophils, eosinophils, and monocytes. Continued daily dosing caused a leukocytosis of up to 10-fold with increases in numbers of circulating neutrophils, eosinophils, monocytes, and lymphocytes. There appeared to be a plateau in the increase in neutrophils in the dose range 3 to 15 μg/kg · d. Marrow aspirates showed increased proportions of promyelocytes and myelocytes. Alternate-day injection of 15 μg/kg maintained a leukocytosis. At doses up to 15 μg/kg · d, rhGM-CSF was well tolerated but adverse effects included bone pains, myalgias, rashes, and liver dysfunction. At doses exceeding 15 μg/kg · d, pericarditis was a dose-limiting toxicity. Idiopathic thrombocytopenic purpura was reactivated by rhGM-CSF in one patient. Conclusions: Bacterially synthesized rhGM-CSF induces a leukocytosis in the dose range of 3 to 15 μg/kg · d. These doses are appropriate for phase II studies.