Interferon has been reported to have activity in the treatment of multiple myeloma. We studied 24 myeloma patients treated with human lymphoblastoid interferon (Wellferon) by intramuscular injection twice weekly at an initial dose of 3 MU/M2 (three patients) or 15 MU/M2 (21 patients). One of 17 evaluable patients achieved a partial remission, three others were stable over a 16-week period of treatment, and 13 others had progressive disease. Subjective toxicity was frequent and substantial, particularly at the 15 MU dose level. Hematologic toxicity was mild and reversible. Two patients experienced acute renal failure. The low rate of response (69c) and substantial level of toxicity fail to support further exploration of these schedules of interferon as a single agent in myeloma.