The acute effects of intraperitoneal lithium on the phosphaturic responses to parathyroid hormone (PTH) and pharmacologic doses of vasopressin were studied in rats. Lithium significantly inhibited the phosphaturic response to PTH at a dosage of 90 mug/kg/hr but did not affect the response to 30 mug/kg/hr. Conversely, lithium eliminated the phosphaturic response to vasopressin at a dosage of 300 mU/kg/hr but did not affect the response to dibutyryl adenosine 3', 5'-monophosphate (db-cAMP), 10 mg/kg/hr. Renal lithium content was increased substantially after the larger dose of PTH and was diminished slightly after db-cAMP and the larger dose of vasopressin. The latter two treatments also inhibited renal lithium reabsorption whereas the smaller dose of vasopressin and both dosages of PTH did not. These results indicate that lithium interferes with the phosphaturic responses to certain dosages of pth and vasopressin and suggest that renal lithium reabsorption and tissue lithium uptake may in part determine the extent of this cation-hormonal interaction. In addition, a competitive type of interaction between lithium and vasopressin is postulated.