Studies were performed in the rat to determine the effect of lithium on electrolyte transport in distal portions of the nephron since steep corticomedullary gradient for lithium has been demonstrated and ionic competition and/or substitution of lithium for sodium and potassium may play a role in inhibition of vasopressin-induced water transport. During the intravenous infusion of LiC1, in the absence of volume expansion and at plasma levels of 2-5 mequiv/liter of Li, maximum urine con-entration was inhibitied. Under the same conditions lithium administration impaired potassium secretion and urinary acidification and resulted in a natriuresis. These results indicate that lithium affects electrolyte transport in the same nephron segments in which the action of vasopressin is inhibitied. In addition, evidence is provided that suggests that during the chronic administration of LiC1, the sustained increase in oral intake of water and urinary flow rate results from an increase in thirst as well as reduced renal concentrating ability.