To determine whether pulmonary and systemic vascular responses to arginine vasopressin (AVP) are altered by hypoxic adaptation, AVP, and, as a control, phenylephrine were administered intravenously in graded doses to pentobarbital anesthetized rats that had been exposed to 10% O2 at ambient pressure or room air for 28 days. After a 30-minute interval, d(CH2)5 Tyr(Me)AVP (130 μg/kg), a specific V1 receptor antagonist of AVP, was injected, and AVP (160 ng/kg) was administered again 5 minutes after injection of d(CH2)5 Tyr(Me)AVP. Mean systemic arterial pressure (MSAP) and mean pulmonary artery pressure (MPAP) were monitored before and after injection of AVP and d(CH2)5 Tyr(Me)AVP. AVP had a significant depressor effect (maximal response = -6.3 ± 0.5 mm Hg following administration of 160 ng/kg AVP) in the pulmonary vascular bed of animals with hypoxic pulmonary hypertension, but no significant effect in normoxic rats. Rats exposed to chronic hypoxia exhibited a blunted systemic pressor response to AVP compared to normoxic rats. In contrast, there were no significant differences in pulmonary and systemic pressor responses to phenylephrine between the hypoxic and normoxic groups. The effects of AVP on MSAP and MPAP were abolished by the specific AVP V1 receptor antagonist, indicating that these effects are V1 receptor mediated. Further study is needed to determine whether AVP is useful in the pharmacologic treatment of hypoxic pulmonary vasoconstriction.