In August 1988 we began a program in which multiple myeloma patients achieving < or = 10% marrow plasma cells and > or = 50% reduction in paraprotein levels after the VAD (vincristine, doxorubicin, dexamethasone) regimen underwent bone marrow harvest, ex vivo marrow purging with 4-hydroperoxycyclophosphamide (4-HC) and marrow cryopreservation. Conditioning with a regimen of high-dose busulfan (total dose 16 mg/kg), cyclophosphamide (120 mg/kg) and melphalan (90 mg/m2) (BU + CY + MEL) followed by autologous BMT was then carried out. Seventeen of the 24 patients who received VAD (71%, 95% confidence interval [CI] 49 to 87%) were eligible for bone marrow harvest. One patient was not harvested because of non-medical reasons; two patients who underwent marrow harvest had gross plasmacytosis present in biopsies performed intraoperatively and did not undergo BMT. Fourteen patients (58%, 95% CI 37 to 78%) received BU + CY + MEL and 4-HC-purged autologous BMT. The median time to recovery of 0.5 x 10(9)/l neutrophils was 19 days (range 14 to 26) while the last platelet transfusion was given on a median of day 32 (range 10 to 46) post-BMT in the evaluable patients. The major non-hematologic toxicity was hepatic; two patients in complete remission died of hepatic veno-occlusive disease. Another patient succumbed to fungal infection despite neutrophil recovery. The remaining 11 patients achieved responses (complete in six and partial in five) associated with a normal performance status.(ABSTRACT TRUNCATED AT 250 WORDS)