The effects of cisplatin (5 mg/kg BW given intraperitoneal^) on renal concentration mechanism were evaluated initially by clearance studies in rats 5–7 days after cisplatin administration and compared to normal rats. During hypotonic saline infusion, cisplatin rats showed a lower inulin clearance (0.56 ± 0.07 vs. 1.12 ± 0.09 ml/min/100gBW, p < 0.01), a higher fractional distal delivery (CNa + CH20/Cin) (36.3 ± 4.4 vs. 22.8 ± 4.5%, p < 0.05), and lower CH20/CNa + CH20 (33.6 ± 5.8 vs. 56.5 ± 5.0%, p < 0.01). During hypertonic saline infusion the TcH20/Cosm was lower in cisplatin (18.3 ± 1.1%) than in normal rats (33.4 ± 3.5%, p < 0.01). These results suggest a defect in NaCl transport in the thick ascending limb of Henle and proximal tubule. In order to characterize these tubular defects, we measured Na-K-ATPase activity {\iM Pi/mg protein/h). In the renal cortex of cisplatin rats the ATPase activity was lower (18.1 ± 3.2) than in normal rats (33.4 ± 6.4, p < 0.05), also in the inner strip of the outer medulla of cisplatin rats Na-K-ATPase was reduced (26.0 ± 5.7) when compared with normal rats (67.3 ± 9.2, p < 0.01), presumably representing a decrease in enzyme activity in the thick ascending limb. In vitro measurements of diffusional water permeability (Pdw) and urea permeability (Purea) of the perfused papillary collecting duct isolated from polyuric cisplatin rats showed that vasopressin (200 uU/ml) added to the bath increased the PDw from 65.4 ± 11.2 to 104.4 ± 12.7 X 10-5cm/s(p < 0.01) and the Purea from 20.1 ± 5.7 to 30.3 ± 8.2 X 10”5cm/s(p < 0.05), as observed in the papillary collecting duct of normal rats. These findings suggest that the polyuric effect of cisplatin is due, at least in part, to impaired NaCl transport of the proximal tubule and thick ascending limb of Henle’s loop. The data rule out the possibility of ADH resistance in the papi