The specific contribution of high-dose carboplatin to regimen-related toxicity after autologous transplantation has been difficult to determine, particularly in patients receiving cyclophosphamide or ifosfamide. We report five cases of severe multi-system failure in patients receiving high-dose carboplatin in addition to other cytotoxics prior to autologous transplantation. Two of these patients did not receive ifosfamide or cyclophosphamide as part of their chemotherapy. The clinical picture consisted of early onset acute renal failure, arrhythmias and/or myocardial hypokinesia, mental obtundation and other neurological deficits and, in two patients, an acute myopathy. In the two patients in whom serum platinum was measured, levels were very high at the time of marrow infusion. All patients had received prior cisplatin therapy but showed either normal or only modestly impaired creatinine clearance before the transplant. These observations are consistent with a specific clinical syndrome associated with carboplatin toxicity and suggest that creatinine clearance may be inadequate as an indicator of potential renal failure when high-dose carboplatin is used.