The aim of this study was to compare the treatment efficacy of mitomycin-C plus tamoxifen (MT) to adriamycin, dibromodulcitol and tamoxifen (DAT) in previously treated patients with metastatic breast cancer. Thirty-two patients with measurable or evaluable disease were entered on the study. Twenty-three were prospectively randomized to receive DAT (Group 1) or MT (Group 2). Nine patients with prior exposure to adriamycin were directly assigned to receive MT (Group 3). Thirty-one patients were evaluable for response and toxicity. The hematological toxicities were comparable among the three treatment groups. DAT gave more nausea and vomiting than MT. One patient developed irreversible fatal congestive heart failure while receiving DAT. The response for Group 1 was 5/11, Group 2, 3/12, and Group 3, 3/8. The duration of response for patients in Group 1 was 455+, 315, 251, 239, 231 days, in Group 2 it was 328+, 144+, 119, and in Group 3 it was 35+, 84, and 112 days. The median time to treatment failure did not differ significantly between Group 1 (114 days), 2 (83 days) and 3 (61 days) (p = 0.24). The median survival time was similar among the three groups (p = 0.41). This pilot study suggests that MT and DAT are both effective treatment programs in patients with metastatic breast cancer who have failed prior chemotherapy regimens.