Eighteen extensively pre-treated patients (35-73 years, median 46) with relapsed multiple myeloma received salvage chemotherapy with 6 g/m2 cyclophosphamide, 800 mg/m2 carboplatin, and 1800 mg/m2 etoposide (CCV) as a 96-h continuous infusion followed by autologous peripheral blood stem cells. The median number of prior chemotherapy regimens was five (range 4-10), including at least one autograft. Four patients died of toxicity, and one developed dialysis-dependent renal failure, while the others tolerated CCV well. Three of six patients with pre-transplant creatinine of > 1 mg/dl died of toxicity compared with one of 12 with creatinine < or = 1 mg/dl (P = 0.083, Fisher's exact test). Three of four patients treated with four previous regimens showed > 50% reduction in tumor compared with one of 14 treated with > 4 regimens (P = 0.02, Fisher's exact test). At the last follow-up, five patients were alive at 8-24 months (median 13) with stable (n = 1) or progressive (n = 4) disease, and nine had died of progressive disease at 2.5-15 months (median 7). We conclude that CCV chemotherapy with autografting is tolerated well by extensively pre-treated myeloma patients provided the pre-transplant creatinine is normal, but toxicity in patients with abnormal renal function is high. The efficacy in multiply relapsed disease is poor, with response in only 22% of patients. CCV may deserve further evaluation early in the course of myeloma in patients with normal renal function.