33 patients with advanced refractory multiple myeloma received a combination of vincristine, cyclophosphamide, carmustine, melphalan and steroids (M-2 protocol). 20 of them had failed prior chemotherapy with alkylating agents and the remaining 13 patients had relapsed after a response to these drugs. An objective tumour cell mass reduction (greater than or equal to 50%) was achieved in 17% of the patients (6% of previously nonresponders and 33% of previously relapsing), while 9 additional patients improved (30-50% tumour reduction), for an overall response rate of 47% (39% for previously nonresponders and 58% for previously relapsing). The median duration of response was 7 months. Thrombocytopenia was the most common toxicity encountered in the study (39% of cases). Our findings indicate that M-2 protocol is an effective salvage treatment for patients who relapse from previous chemotherapy with alkylating agents. In contrast, results in patients who are primarily resistant to these drugs justify the search for different treatment programmes which can produce greater degrees of tumour reduction.