Aquaporin-2 (AQP-2) encodes the vasopressin-regulated "water channels" of the renal collecting duct and is excreted in human urine. We measured urinary excretion of AQP-2 by radioimmunoassay in 15 term and 10 preterm infants on day 1 and day 4 of life to determine the molecular basis of water balance during the newborn period. AQP-2 was detectable in the urine of term and preterm newborns, but AQP-2 excretion was severalfold less than the reported level in normal adults. Urinary excretion of AQP-2 significantly decreased postnatally, in parallel with a reduction in urine osmolality and arginine vasopressin (AVP) excretion. Urinary AQP-2 correlated positively and significantly with urine osmolality on days 1 and 4 and with AVP on day 1 in both groups. No significant differences were detected in AQP-2 levels between term and preterm newborns. Our findings suggest that vasopressin-regulated water channels are expressed in the renal collecting duct of both term and preterm newborns, although to a lesser extent as compared with adults, and these channels encoded by AQP-2 contribute to the urine concentrating power of the newborn kidney.