A group of 46 patients with melphalan-resistant multiple myeloma was treated according to the M-2 protocol with melphalan, prednisolone, BCNU, cyclophosphamide, and vincristine. According to the Salmon and Durie classification, four patients had stage II A; 36, stage III A; and six, stage III B disease. Treatment resulted in five patients (11%) entering remission, while 21 (46%) had stable and 20 (43%) had progressive disease. The median survival for all patients was 12.5 months, patients in remission surviving longer (median 46 months) than those with stable disease (median 15.4 months) or progressive disease (median 6.9 months). Compared with other treatment regimens used in melphalan-resistant myeloma, the remission rate is low but the median survival exceeds that reported by most other authors.