Combined gentamicin-cephalothin therapy in four patients after treatment with cis-dichlorodiammineplatinum(II) (CPDD) for advanced solid tumors was complicated by severe acute renal failure. The total dose of gentamicin varied from 240 to 945 mg and that of cephalothin varied from 28 to 48 g. Low-dose (0.5 mg/kg x 8) CPDD was given to one patient, high-dose (3 mg/kg) CPDD was given to two patients, and very high-dose (5 mg/kg) CPDD was given to one patient. The high and very high doses of CPDD were given with concomitant mannitol diuresis. CPDD therapy was complicated by mild transient azotemia in three patients and by severe acute renal failure in one. In the latter, the azotemia began to improve on Day 7 after CPDD treatment. Following gentamicin-cephalothin therapy, all patients developed severe acute renal failure which persisted until death. At autopsy, all patients had extensive renal tubular necrosis at various stages. These findings indicate that gentamicin-cephalothin therapy after treatment with CPDD can be severely nephrotoxic, and that this antibiotic combination should be given with great caution, if at all, to patients receiving CPDD treatment for malignancy.