From October 1983 until December 1986, 164 patients with multiple myeloma stage II-III were included in a prospective randomized multi-centre study comparing melphalan-prednisone (MP) with multidrug chemotherapy (MDC). The patients comprised 77% of all newly diagnosed myeloma stage II-III cases reported from 18 hospitals covering the entire Health Care Region of Western Sweden (1.5 million inhabitants). Patients randomized to MP (29 stage II and 55 stage III patients) were given oral melphalan and prednisone every 6 weeks. For patients randomized to MDC, stage II patients (n = 25) were given VMCP every 4 weeks and stage III patients (n = 53) VBAP and VMCP alternately every 4 weeks. For stage II patients, the response rate for MP compared to VMCP was 69 versus 56% and the median survival 46 versus 33 months. For stage III the response rate for MP compared to VBAP/VMCP was 58 versus 57% and the median survival 26 versus 24 months. No statistically significant differences were seen. The time to response and remission duration were also similar in both treatment arms. The dose intensity index (cumulative given/planned dose of myelosuppressive drugs) was greater than or equal to 0.8 in 89% of the MP patients and 81% of the MDC patients. Patients with index values less than 0.8 had the same response rate as patients with index greater than or equal to 0.8. This study has not demonstrated any advantage of MDC over traditional MP in multiple myeloma stage II-III.