Intermediate-dose (25 mg/m2) intravenous melphalan has been evaluated in 34 multiple myeloma patients refractory to standard chemotherapies. The median time from diagnosis to entering of patients into the study was 27 months (range 7-71 months). A response was obtained in 12/34 patients (35%). 4 of 12 responding patients have relapsed and 2 of these have died; 8 responders have not relapsed and are still alive. The median duration of survival after 28 months of follow-up has not yet been reached in the group of patients responding to treatment. However, the overall median duration of survival for the 34 patients entered into the study was 8 months. The median duration of response was 16 months. Toxicity was limited to leukopenia, thrombocytopenia, nausea and vomiting. This lack of severe toxicity allowed us to administer the drug on an outpatient basis. The response rate and the low toxicity observed in this group of patients are encouraging and suggest that intermediate-dose intravenous melphalan is an effective and safe second line treatment for patients with multiple myeloma not responding to conventional treatment.