Six patients with hairy cell leukemia (HCL) and neutropenia (median neutrophil count 563/microliters, range 30-1200) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) at a dose of 5 micrograms/kg by daily subcutaneous injection as an adjunct to interferon-alpha (IFN-a) therapy, in order to ameliorate neutropenia. Five of six patients responded to G-CSF with normalization of neutrophil counts (> 1800/microliters) within 2-11 days and a median neutrophil count of 5211/microliters (range 4312-10160) at the end of G-CSF therapy. In three of these patients, infections resolved when neutropoiesis recovered. In one patient with very severe neutropenia (30/microliters), in whom myeloid progenitors were not detectable, G-CSF therapy failed to restore granulopoiesis. Cessation or interruption of G-CSF after 2-5 weeks of therapy resulted in a rapid decline of neutrophil counts to lower or subnormal levels (median value 1478/microliters, range 770-2739) within 1 week, suggesting that the improvement of granulopoiesis was dependent on G-CSF and not due to IFN-a therapy. G-CSF may be a useful adjunct to IFN-a therapy in patients with HCL in order to manage or prevent neutropenic complications in the early phase of treatment.