Micropuncture and clearance studies were performed on normal untreated and polyuric lithium chloride treated rats (10–12 days). A persistent hypernatremic state quickly developed in the polyuric lithium treated rats during hydropenia resulting from an increased urinary loss of water over sodium chloride, as the fractional excretion of sodium remained at control levels. Superficial proximal tubule and loop of Henle fluid reabsorption was depressed by 8 and 17%, respectively, in lithium-treated rats during this period. By contrast, water reabsorption in the distal tubule and collecting rystem was significantly increased in the lithium animals, being 27% of the filtered load compared with 20% in normal sats. These results suggest that the urinary-concentrating defect induced by lithium treatment is due primarily to a depression of proximal tubule and possibly loop of Henle function, and that water reabsorption within the distal nephron may in fact be augmented; thus it is unlikely that the action of antidiuretic hormone is significantly impaired. Marked phosphaturia and hypocalciuria were also noted in the lithium-treated rat