We treated 16 patients in a phase I trial of escalating doses of intravenous cisplatin in combination with the chemoprotectant glutathione given every 21 days. Forty-three of 44 cycles (98%) were evaluable, 85% of cycles were given on time, and the median number of cycles per patient was 2. Dose-limiting nephrotoxicity was reached at a dose of 175 mg/M2 of cisplatin. Other toxicities included ototoxicity in 7 patients (44%) and grade 3 to 4 nausea and vomiting in 15 evaluable cycles (34.9%). Myelosuppression was infrequent. An increase to 175% of standard cisplatin dose intensity is attainable with the administration of glutathione; however, toxicity is substantial and the number of tolerated cycles is limited. Alternatives to the single bolus dose schedule studied in the present trial should be explored in order to better define the clinical utility of glutathione in combination with high-dose cisplatin.