α- and β-MSH produced a marked natriuretic effect when injected ip in trained, fasted water-loaded rats. Doses of 50 and 90 μg of β-MSH produced a significant natriuresis, kaliuresis, and no change in urine output. Doses of 5, 10, and 50 μg of α-MSH produced a doserelated natriuresis, kaliuresis, and antidiuresis. The low doses of 1 and 2 μg of α-MSH also produced a significant increase in Na+ excretion without affecting K+ excretion or urine output. Since the natriuresis outpaced the kaliuresis, the Na+/K+ ratio increased. A 100 mU dose of oxytocin induced natriuresis, kaliuresis and a slight antidiuresis. The dose of 0.5 mU of lysinevasopressin produced a significant natriuresis and kaliuresis in the 20-40 min sample after injection, but the 1 mU dose was natriuretic and kaliuretic only in the 40-60 min sample. Both doses produced a significant antidiuresis. Treatment with thioglycollate to inactivate any vasopressin or oxytocin contaminating the α-MSH did not alter the natriuretic effect but eliminated the antidiuresis. Since thioglycollate eliminated the natriuretic effect of oxytocin, it is concluded that α- and β- MSH possess natriuretic activity in the rat. (Endocrinology90: 700, 1972)