A current southeastern cancer study group protocol for the treatment of multiple myeloma involves induction with BCNU, cyclophosphamide, and prednisone (BCP) and maintenance with either melphalan and prednisone (MP), prednisone, Adriamycin, imuran, and vincristine (PAIV), or delayed treatment of relapsed cases following induction. These combinations of drugs are used as induction regimens to establish their chemotherapeutic effects and hematological toxicity in the murine MOPC 104E plasmacytoma model. The three combinations of drugs produce rapid, reliable, and reproducible tumor regressions. However, MP is the only combination which consistently gives long-term disease-free survivors. This particular regimen has least toxicity and is considered to be most effective. BCP produces complete remission with no relapses; however, long-term survivors are not observed with this combination due to early deaths because of drug toxicity. Most of the mice on the PAIC regimen die due to drug toxicity. This combination is considered least effective. With the different drug regimens, toxic events and regressions are noted to occur at different time periods, indicating that perhaps tumor cells in different stages are being destroyed. Toxic events as measured by hematocrit and body weight changes always precede regression by several days. This disparity between rapid drug effects on the host and a delayed effect on the tumor remains unexplained but may possibly be used to advantage in designing future trials.