Cis-Diammine-1,1-cyclobutanedicarboxylate platinum(II) (CBDCA, JM8) is a nonnephrotoxic analog of cisplatin currently undergoing clinical evaluation. Pharmacokinetic studies were performed in patients receiving CBDCA (20-520 mg/sq m) as a 1-h infusion without hydration or diuresis. Following the end of infusion plasma levels of total Pt and ultrafilterable (MW < 50,000) Pt (free Pt) decayed biphasically [t1/2 - half-life] with 1st-order kinetics (total Pt t1/2.alpha. = 98 min; t1/2.beta. range, 399 to > 1440 min; free Pt t1/2.alpha. = 87 min; t1/2.beta. = 354 min). During the first 4 h, binding of Pt to plasma protein was limited (24%), with most of the free Pt in the form of unchanged CBDCA (94%). However, by 24 h, the majority of Pt was protein bound (87%). The major route of elimination was renal, 65% of the Pt adminstered being excreted in the urine within 24 h, with 32% of the dose excreted was unchanged CBDCA. No evidence was found from studies on the renal clearance of free Pt to indicate renal tubular secretion (mean free Pt renal clearance, 69 ml/min). However, the plasma clearance of free Pt did correlate postively with glomerular filtration rates (P = 0.005). None of the pharmacokinetic parameters determined were dose-dependent. In vitro studies with plasma and urine demonstrated that, in contrast to cisplatin, CBDCA is a stable complex [t1/2 - 37.degree.; plasma, 30 h, and urine (range), 20-460 h]. The differences in the pharmacokinetics of cisplatin and CBDCA may explain why the latter complex is not nephrotoxic.