A prospective Phase II trial of combination chemotherapy in patients with metastatic carcinoid tumors was conducted by the Southwest Oncology Group. The therapy included 5-fluorouracil, Adriamycin, cyclophosphamide, and streptozotocin (FAC-S) or the same combination without Adriamycin (FC-S) in patients with heart disease. Seventy-four patients were entered and two were ineligible. Sixty-nine of the 72 were histologically reviewed. Six patients were declared ineligible after this review. Fifty-six patients received FAC-S, and nine received FC-S (one patient was inevaluable). The response rates were 31% and 22%, respectively. The median survival of all patients was 10.8 months. The analyses of various clinical and histologic parameters indicated that responses were more common in patients with gastrintestinal carcinoids; there was also a tendency toward shorter survival in patients with tumors that had a higher mitotic rate or the atypical and/or undifferentiated histologic pattern. The FAC-S combination can produce objective responses in patients with metastatic carcinoid tumors, but these are generally partial and brief. It was also concluded that currently available chemotherapy is inadequate.