From September 1975 to December 1981, 63 consecutive untreated patients with multiple myeloma received the Lee M-2 protocol. We used the same drugs (melphalan, cyclophosphamide, vincristine, BCNU and prednisone) but employed the lowest suggested doses and recycled earlier, i.e. after 21-28 days. Thirty-five patients (62.5%) were in stage III, 16 (28.6%) in stage II and 5 (8.9%) in stage I. An objective response (reduction in paraprotein production rate greater than 50%) was obtained in 44 out of 56 cases (78%); 32 (57%) had a reduction greater than 75%. The median duration of response was 21.5 months. In responding patients the treatment was stopped after 1 yr and resumed only at relapse. Twenty-two out of 25 retreated patients are now evaluable. Eighteen of them (82%) responded again; in retreatment the degree of response was lower, but the duration of second response was only slightly lower than the first response (15.7 vs 21.5 months, NS). Of 7 patients receiving a third M-2 reinduction 4 responded again. The median survival for all the patients is 51 months. The high rate of second response to the M-2 regimen after an unmaintained remission brings into question the value of continuous therapy in responsive multiple myeloma.