Cisplatin (cis-diamminedichloroplatinum II), a chemotherapeutic agent used against epithelial neoplasms, is known to cause hypomagnesemia and renal magnesium wasting. In order to further characterize the effect of multiple doses of this drug upon serum magnesium levels and renal magnesium handling, we prospectively studied 28 patients who received a total of 82 doses of cisplatin. All patients developed hypomagnesemia that was dose-related (r = .66, P less than .001, n = 101); the lowest serum magnesium level reached in individual patients ranged from 0.3 to 1.7 mg/dL. Renal magnesium wasting was documented in 19 patients, with urinary fractional excretion of magnesium ranging from 2.9% to 22.3% despite serum magnesium levels of greater than or equal to 1.5 mg/dL. Evidence of renal tubular injury (renal tubular epithelial cells or tubular cell casts) was detected in 47 of 47 urine sediment examinations performed two to four days after cisplatin administration. There was no clear evidence that cisplatin caused defects in renal handling of electrolytes other than magnesium; in fact, 16 of the 28 patients demonstrated avid renal reabsorption of one or more other electrolytes despite significant magnesium wasting. We conclude that cisplatin alters renal tubular handling of magnesium, resulting in significant prolonged dose-related hypomagnesemia.