The relation between urine flow (V), lithium clearance (CLi) and sodium clearance (CNa) was studied in rats given food containing lithium in amounts leading to inhibition of distal reabsorption of water and sodium. Maximum inhibition of the reabsorption of water was reached at serum lithium concentrations of about 1 mM. At higher serum lithium levels the rats developed intoxication due to a lowering of CLi and a consequent rise of the serum lithium concentration. The intoxication was characterized by a proportional decrease of V and CLi. The decrease of V and CLi was not related to changes of CNa. The results indicate that lithium is reabsorbed in the proximal tubules in parallel with sodium and that the lowering of CLi is due to increased fractional proximal reabsorption of lithium and sodium compensatory to inhibition of the distal reabsorption of sodium.