The pharmacokinetics of total plasma platinum (TP), ultrafilterable plasma platinum (UF) and urinary excretion were studied in 15 patients receiving 2 consecutive 6-hour intravenous infusions of cisplatin (80 to 100 mg/m2) at a dose interval of 3 weeks. After first drug exposure, TP was slowly eliminated from plasma [terminal half-life (t½&ggr;) of 11.6 ± 2.5 days]. On second drug exposure, the mean plasma clearance and volume of distribution at steady-state decreased significantly (p<0.001) from 0.15 to 0.11 L/h/m2and from 49.5 to 42.1 L/m2, respectively, but no significant change was observed in the t½&ggr;(11.6 to 12.6 days) or in the mean residence time (14.6 to 16.3 days). A significant linear correlation was found between observed and predicted plasma levels of TP during the second course. The mean peak UF levels, the area under the concentrationvstime curve from zero to infinity (AUC0-∞) and urinary excretion (0 to 24 hours) were not significantly different between the 2 courses. The extent of reduction in plasma clearance of TP over 3 drug infusions in 3 evaluated patients correlated with the development of ototoxicity.