Treatment with continuous infusions of cisplatin results in increased filterable drug exposures as measured by the area under the curve (AUC) of nonprotein-bound plasma platinum levels. To determine the dose-limiting toxicity and optimal method of administration, 24 patients were treated with continuous infusions of cisplatin at a dose rate of 25 mg/M2/day in a limited Phase I trial. A total of 47 courses were given. Nine patients received 13 courses of 4 days duration, 19 received 29 courses of 5 days duration, and five received courses of 6 or 7 days duration. Dose-limiting toxicity was found to be leukopenia: 42% of patients receiving the 5-day treatment developed a nadir count of less than 3000 cells/mm3. Nausea and vomiting were easily controlled. Minimal nephrotoxicity occurred in five patients and was associated with daily volume expansion with 2 l of 0.9% NaCl solution in four patients. All other patients were given 3 l of daily volume expansion during treatment. Responses were seen in 6 of 22 evaluable patients (27%). It is concluded that continuous infusion cisplatin at a dose rate of 25 mg/M2/day can be given safely for 5 days as a single agent if concomitant volume expansion with at least 3 l of 0.9% NaCl solution is given daily. Phase III comparative trials with a conventional bolus and newer high-dose regimens for response and toxicity are indicated.