The effect of three cycles of high-dose cisplatin (40 mg/m2 day for 5 days) on renal tubular function was evaluated in 30 patients. A significant impairment of proximal tubular salt and water reabsorption rates was observed, but also distal tubular function seemed to be affected. These changes were also present 6 months after termination of treatment. Sodium and magnesium clearance increased significantly during treatment. Magnesium clearance normalized shortly after treatment but sodium clearance was significantly elevated 6 months after treatment. Proteinuria, albuminuria, and amino aciduria, together with an increase of beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) excretion rates, were observed during each treatment cycle. A good correlation was registered between the increase in urinary excretion rates of protein, NAG, and magnesium and the decrease in proximal tubular salt and water reabsorption during cisplatin administration.