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In a phase I study, the sequentially administered combination of recombinant human interleukin-3 (rhlL-3) and rhGM-CSF was compared with treatment with rhlL-3 alone in 15 patients with advanced tumors but normal hematopoiesis. Patients were initially treated with rhlL-3 for 15 days. After a treatment-free interval, the patients received a second 5-day cycle of rhlL-3 at an identical dosage, immediately followed by a 10-day course of rhGM-CSF, to assess the toxicity and biologic effects of this sequential rhlL-3/rhGM-CSF combination. rhlL-3 doses tested were 125, and 250 μg/m2, whereas rhGM-CSF was administered at a daily dosage of 250 μg/m2Both cytokines were administered by subcutaneous (SC) bolus injection. rhlL-3/rhGM-CSF treatment was more effective than rhlL-3 but equally effective to each other in increasing peripheral leukocyte counts, especially neutrophilic and eosinophilic granulocyte counts. In contrast, both modes of cytokine therapy raised the platelet counts to the same degree. rhlL-3/GM-CSF treatment was more effective than rhlL-3 in increasing the number of circulating hematopoietic progenitor cells BFU-E and CFU-GM. High-dose rhIL-3, but not low-dose rhlL-3, was as effective as the rhlL-3/rhGM-CSF combinations in increasing the number of circulating CFU-GEMM. The increase in absolute neutrophil counts correlated with the increase in the number of circulating CFU-GM. Side effects, mainly fever, headache, flushing, and sweating, were generally mild, but in two patients the occurrence of chills, rigor, and dyspnea after initiation of GM-CSF treatment necessitated dose reduction and discontinuation, respectively. These results indicate that sequential treatment with rhIL-3 and rhGM-CSF is as effective as single-factor treatment with rhlL-3 in stimulating platelet counts, whereas the effect of combination therapy on neutrophil counts and circulating progenitor cells is superior.