Four anticancer drugs with cell cycle phase specific characteristics (azathioprine, cytosine arabinoside, hydroxyurea and vincristine) were individually used to treat 12 patients with multiple myeloma in partial remission (i.e. > 50% reduction in tumor cell number) after cell cycle nonspecific chemotherapy. In 6 of 8 patients vincristine induced further statistically significant reductions in total body myeloma cell number (24-60% tumor cell reduction), whereas, azathioprine had lesser activity. Cytosine arabinoside and hydroxyurea were unsuccessful and excessively toxic chemotherapeutic agents in this setting, although optimal dosing schedules were difficult to achieve because they caused moderately severe bone marrow suppression. Vincristine is a useful cytoreductive agent for multiple myeloma and should be added to cell cycle nonspecific agents for the treatment of this disease.