The safety and optimal dose and schedule of stem cell factor (SCF ) administered in combination with filgrastim for the mobilization of peripheral blood progenitor cells (PBPCs) was determined in 215 patients with high-risk breast cancer. Patients received either filgrastim alone (10 μg/kg/d for 7 days) or the combination of 10 μg/kg/d filgrastim and 5 to 30 μg/kg/d SCF for either 7, 10, or 13 days. SCF patients were premedicated with antiallergy prophylaxis. Leukapheresis was performed on the final 3 days of cytokine therapy and, after high-dose chemotherapy and infusion of PBPCs, patients received 10 μg/kg/d filgrastim until absolute neutrophil count recovery. The median number of CD34⁺ cells collected was greater for patients receiving the combination of filgrastim and SCF, at doses greater than 10 μg/kg/d, than for those receiving filgrastim alone (7.7 v 3.2 × 10⁶/kg, P < .05). There were significantly (P < .05) more CD34⁺ cells harvested for the 20 μg/kg/d SCF (median, 7.9 × 10⁶/kg) and 25 μg/kg/d SCF (median, 13.6 × 10⁶/kg) 7-day combination groups than for the filgrastim alone patients (median, 3.2 × 10⁶/kg). The duration of administration of SCF and filgrastim (7, 10, or 13 days) did not significantly affect CD34⁺ cell yield. Treatment groups mobilized with filgrastim alone or with the cytokine combination had similar hematopoietic engraftment and overall survival after PBPC infusion. In conclusion, the results of this study indicate that SCF therapy enhances CD34⁺ cell yield and is associated with manageable levels of toxicity when combined with filgrastim for PBPC mobilization. The combination of 20 μg/kg/d SCF and 10 μg/kg/d filgrastim with daily apheresis beginning on day 5 was selected as the optimal dose and schedule for the mobilization of PBPCs.