Studies using fetal sheep, goats, and guinea pigs indicate that vasopressin may play a role in preparing the fetal lung for the transition from a uterine to an air-breathing environment by slowing lung liquid secretion. The mechanism of vasopressin action is believed to occur through V2 receptors with subsequent activation of amiloride-sensitive sodium channels. However, the presence of the V2 receptor in human lung has not yet been documented. In the present study, expression of the vasopressin V2 receptor in fetal and adult human lung was examined using reverse transcription-polymerase chain reaction (RT-PCR), Northern blot analysis, and DNA sequencing. Using RT-PCR and primer pairs specific for the human V2 receptor, PCR products of the predicted sizes of 512 and 862 bp were obtained from adult human lung. DNA sequencing of the cloned PCR products revealed exact identity with the published sequence for the V2 receptor. Northern blot analysis revealed the expression of a approximately 1.9 kb mRNA in adult human lung as well as in kidney, but not in fetal human lung at 22-24 weeks of gestation. However, using the more sensitive RT-PCR assay the 862-bp product was successfully amplified from human fetal lung, although the data indicate the mRNA for this receptor is expressed in lower levels than in adult human lung or kidney. Using RT-PCR and primers specific for the rat V2 receptor, a PCR product of the predicted size of 461 bp was amplified from adult rat lung and kidney, despite an earlier report that this receptor mRNA is absent from the lung of this species. The role for the V2 receptor in adult human lung is unknown at this time, but, as in the human kidney and lungs of fetal sheep, goats, and guinea pigs, this receptor may play a role in fluid balance.