An alternating VCAD-VAD regimen, combining vincristine-doxorubicin by continuous infusion with cyclophosphamide and pulse dexamethasone, or VAD alone, was given to 175 previously untreated patients with multiple myeloma. The response rate with primary VAD-based regimens of 55% was virtually identical to the 54% in comparable patients treated previously with similar programs by using bolus vincristine-doxorubicin. Despite responses to VAD that were more rapid in onset than any previous treatment, remission and survival times were similar. This may be due to major differences in drug sensitivity between progenitor and differentiated plasma cells. A VAD-based regimen seems better for newly diagnosed patients when rapid control of multiple myeloma is necessary.