Clinical outcomes were assessed in 68 consecutive patients with multiple myeloma of high or intermediate tumor mass that had responded to VAD or dexamethasone-based therapy and were consolidated with early intensive therapy and autologous stem cell transplantation. Results were compared with those of 50 comparable patients who refused or were unable to receive intensive treatment for socioeconomic reasons. Following high-dose therapy, the rate of CR increased from 6 to 37%, with median survival prolonged by 10 months. Survival of 21 patients with disease converted from PR to CR (median 8.3 years) was significantly longer than that of similarly-treated patients who remained in PR (median 5.0 years). CR of myeloma represents the major surrogate marker of long survival and the primary goal of myeloablative treatment for patients in PR. Twelve of 18 patients with rapid reduction of myeloma protein (T(1/2) < 0.5 months), and myeloma protein reduction to <1.0 g/dl after primary therapy achieved CR (67%), identifying pretransplant features favorable to intensive therapy. Among 35 patients with slower reduction or higher residual myeloma protein, CR occurred in eight patients (23%) (P < 0.01), for whom other treatments should be considered. The kinetics of response to initial therapy should be considered in selecting patients more likely to achieve CR and consequent long survival after intensive treatment.