In an attempt to examine the possibility of decreased toxicity in patients with advanced breast cancer who had not previously received chemotherapy, 33 women were given combination chemotherapy consisting of mitomycin C (10 mg/m2) every 6 weeks and mitoxantrone (6 mg/m2) every 3 weeks. The patients had predominantly visceral disease and received a median of two cycles of therapy. Of the 32 evaluable subjects, 15 (47%) achieved a partial response lasting a median of 7 months. Hematological toxicity was generally mild, although there were two episodes of sepsis. One patient developed hemolytic-uremic syndrome, and one subject developed pulmonary fibrosis, both presumably attributable to treatment with mitomycin C. Another patient died of hepatic failure (hepar lobatum). Thus, there were five patients who sustained life-threatening toxicities; this may have been due to the poor performance status and advanced age of some of the patients. Gastrointestinal toxicity and alopecia were minimal. Patient acceptance was high and there was an improvement in symptomatology in the majority of patients. In conclusion, mitomycin C and mitoxantrone chemotherapy is an active drug combination for the treatment of advanced breast cancer that seldom causes significant distressing gastrointestinal side effects or alopecia; however, the duration of response to this regimen appears to be shorter than that obtained with either cyclophosphamide - methotrexate - 5-fluorouracil (CMF) or cyclophosphamide - Adriamycin - 5-fluorouracil (CAF) combination chemotherapy.