Nephrotoxicity, the dose-limiting toxicity of cis-diamminedichloroplatinum(II) (CDDP), is ameliorated when administered in hypertonic saline with normal saline hydration. To determine whether the diminished nephrotoxicity is associated with alteration of the pharmacokinetics of CDDP, we examined the pharmacokinetics of free and total platinum, platinum renal excretion, and urine electrolytes in patients given CDDP in hypertonic saline and in patients given CDDP in a conventional manner. The pharmacokinetics of free and total platinum for equal doses of CDDP were similar regardless of the vehicle of administration and the method of hydration. CDDP given in a vehicle of high chloride concentration with normal saline hydration resulted in a statistically significant increase in both urine volume and chloruresis compared to the conventional regimen. The decreased nephrotoxicity associated with administration of CDDP in hypertonic saline with saline diuresis may be related to increased chloruresis, urinary volume, or a combination of both, but did not appear to be related to an alteration in the pharmacokinetics.