Cisplatin (CIS-diamine dichloroplatinum) is a highly nephrotoxic antineoplastic agent which may cause acute renal failure and renal tubular dysfunction. In the present study we have examined the effect of chronic cisplatin administration on sodium-dependent <sup>32</sup>P-phosphate and <sup>3</sup>H glucose transport by the renal brush border membrane vesicles (BBMV). Our results indicate that both transport mechanisms were significantly reduced at the BBMV following cisplatin therapy due to an increased K<sub>m</sub> (0.13 ± 0.09 vs. 0.34 ± 0.09 m M; p= < 0.01) without significant change in Vmax (56 ± 18 vs. 44 ± 17 p M/mg/s). The results of these studies indicate that cisplatin causes a diffuse renal injury in the proximal segment of the nephron altering both transport mechanisms. Possible mechanisms of cisplatin nephrotoxicity are discussed.