We compared the effect of combined natural interferon-alpha (HLBI)/VCAP chemotherapy with VCAP chemotherapy alone on multiple myeloma. Sixteen previously untreated patients with multiple myeloma were treated with a combination of IFN-alpha and VCAP chemotherapy; nine of them were treated with HLBI-VCAP (I) regimen (HLBI 3 x 10(6) units/day, daily, 56 days) only for induction chemotherapy, and seven with continuous HLBI-VCAP (II) regimen (HLBI 3 x 10(6) units/day, twice a week) both for induction and maintenance chemotherapy. Thirty-one control patients were treated with a VCAP regimen only. HLBI-VCAP (II) regimen exhibited an 85.7% (6/7) response rate, while VCAP and HLBI-VCAP (I) regimen showed 74.2% (23/31) and 77.8% (7/9) response rates, respectively. The median duration of survival was 43 months in the control group, greater than 44 months in HLBI-VCAP (I) group and greater than 45 months in HLBI-VCAP (II) group. No significant difference in survival duration has yet been observed between the VCAP group and HLBI-VCAP groups. We conclude that continuous, long-term combination therapy with HLBI and VCAP regimen for induction and maintenance therapy may be most effective, and found that intensive HLBI-VCAP regimen, for only remission induction therapy, was not more effective than VCAP regimen alone.