Nine pediatric patients (median age, 8 years; range, 0.7 to 19 years), eight with refractory aplastic anemia and one with newly diagnosed aplasia, were enrolled in a phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) administered via continuous intravenous infusion. Doses ranged from 8 to 32 micrograms/kg/d. Six of eight evaluable patients responded with a significant rise in neutrophil count (median fourfold increase; range, 2.5- to 31-fold) during the 28-day induction period. Five patients completed 2 further months of therapy (maintenance) with persistent or improved neutrophil responses. Three patients had bone marrow aspirates suggestive of increased erythropoiesis, although only one patient had improvement in peripheral hematocrit and platelet count. In the five patients completing maintenance, three experienced a rapid return to baseline counts after rhGM-CSF was discontinued, one maintained a neutrophil response for 2 months after drug discontinuation, and one has maintained a trilineage response for greater than 1 year off study. Drug therapy was well tolerated. Toxicity was minimal at doses from 8 to 16 micrograms/kg/d. Fever and rash were more commonly seen at 32 micrograms/kg/d. No patient developed an infection during the course of rhGM-CSF administration. These results demonstrate that rhGM-CSF increases peripheral neutrophil counts in children with refractory and newly diagnosed aplastic anemia and may be able to stimulate a multilineage response in a more limited number. Randomized, prospective trials are necessary to determine if rhGM-CSF administration will impact favorably on the morbidity and mortality of severe aplastic anemia.