Several problems in the management of life-threatening mucormycosis remain unresolved, necessitating new methods of management. Four patients with histopathologically proven rhinocerebral mucormycosis were treated with high cumulative doses of granulocyte colony-stimulating factor (G-CSF). All had multiple predisposing factors for mucormycosis, particularly leukemia and neutropenia. Two patients refractory to fluconazole therapy were treated with liposomal amphotericin B. The improvement in clinical manifestations was closely related to neutrophil recovery, and all patients were alive at the end of therapy. In addition to surgical debridement and antifungal therapy, G-CSF seems to have played a role in their survival.