Substantial increases in dose-intensity of chemotherapy yield a severalfold increase in complete remission rates and durable responses in several types of malignant disease. Hematopoietic colony-stimulating factors decrease the duration of the resultant severe neutropenia but optimal dosing regimens of these cytokines have not yet been determined. This study was designed to explore the use of both yeast-derived and E. coli-derived GM-CSF given pre- and postchemotherapy with an intensive combination chemotherapy regimen. The chemotherapeutic regimen consisted of cyclophosphamide 5000 mg/m2, etoposide 1500 mg/m2, and cisplatin 150 mg/m2 (DICEP). Patients receiving either yeast-derived GM-CSF (6.5 days) or E. coli-derived GM-CSF (6.0 days) had a shorter duration of severe granulocytopenia with an absolute granulocyte count below 300/microL than patients receiving no GM-CSF (11.0 days, p = 0.0001). Administration of GM-CSF for 6 days immediately preceding DICEP did not further shorten the duration of cytopenia. E. coli-derived GM-CSF given at doses above 5 micrograms/kg was poorly tolerated and offered no hematologic advantage. Lower doses (3 micrograms/kg) of the E. coli product were better tolerated but still produced more toxicities than yeast-derived GM-CSF. The yeast-derived product produced no local skin reactions and decreased the incidence of nonhematologic and all grade 3 or 4 toxicities compared to the control group.