The effects of glucagon on water and electrolyte transport in the kidney were investigated on hormonedeprived rats, i.e. thyroparathyroidectomized diabetes insipidus Brattleboro rats infused with somatostatin. Glucagon consistently inhibited the reabsorption of water and Na +, CI-, K Β§ and Ca 2 Β§ along the proximal tubule accessible to micropuncture, leaving the reabsorption of inorganic phosphate (Pi) untouched. In the loop, besides its previously described stimulatory effects on Na +, CI-, K +, Ca z+ and Mg 2+ reabsorption, glucagon strongly inhibited Pi reabsorption, very probably in the proximal straight tubule. These effects resulted in a significant phosphaturia and considerable reductions of Mg 2+ and Ca z + excretions. The effects of glucagon at both the whole kidney and the nephron levels are very similar to those previously described for calcitonin. In the absence of an adenylate cyclase system sensitive to glucagon and calcitonin in the rat proximal tubule, and from the analogy of their physiological effects with those elicited by parathyroid hormone, it is suggested that glucagon and calcitonin exert their inhibitory effects on Na and Pi reabsorption in the proximal tubule through another pathway, which could be the phosphoinositide regulatory cascade.