Newborns show an inability to concentrate maximally their urine. The vasopressin responsiveness of adenylate cyclase was, therefore, examined in membranes obtained from kidneys of neonatal and adult rats and from renal medulla and isolated collecting tubules of newborn and adult rabbits. In spite of higher basal and NaF-stimulated activity, vasopressin failed to stimulate adenylate cyclase from neonatal rat kidneys. In neonatal and adult rabbits, basal and NaF-stimulated adenylate cyclase activities of renal medullary membranes were comparable but vasopressin stimulation was significantly lower in the newborns. No change in hormonal activation constant was observed. This hyporesponsiveness of neonatal adenylate cyclase to vasopressin was confirmed with single isolated rabbit collecting tubules for adenylate cyclase determination, a highly sensitive preparation. It is intriguing to speculate that the low vasopressin stimulation of the medullary adenylate cyclase in the developing kidney may contribute to the known limitations of the urinary concentrating mechanism in the newborn period.