The effects of adenosine on plasma arginine vasopressin (AVP) concentrations were determined in chronically catheterized fetal sheep (> 0.8 term). Infusion of adenosine [0.35 +/- 0.01 (SE) mg.min-1.kg-1] into the inferior vena cava of six fetuses caused a transient fall in arterial PO2 (by approximately 3 Torr), a slight reduction in arterial pH, and a 5- to 6-mmHg decrease in diastolic pressure without significantly affecting systolic or mean arterial values. A lower rate of infusion (0.19 +/- 0.01 mg.min-1 x kg-1) in five fetuses had virtually no effect on arterial blood gases, pH, or arterial pressures. Both the low- and high-dose adenosine infusions significantly increased fetal plasma AVP concentrations (1.7 +/- 0.2 to 25 +/- 7 pg/ml and 1.6 +/- 0.1 to 54 +/- 8 pg/ml, respectively). Intravenous infusion of papaverine lowered fetal diastolic and mean arterial pressures by approximately 8 mmHg but had no significant effect on plasma levels of AVP. During an hour of isocapnic hypoxia (arterial PO2 12-13 Torr), fetal plasma AVP levels increased from 1.7 +/- 0.2 to 40 +/- 6 pg/ml. Intra-arterial infusion of the adenosine receptor antagonist 8-(p-sulfophenyl)-theophylline significantly blunted the hypoxia-induced rise in plasma AVP concentrations to a maximum mean level of 11 +/- 6 pg/ml. These results indicate that 1) adenosine causes a dose-dependent increase in plasma AVP concentrations and 2) a hypoxia-induced rise in fetal adenosine levels triggers vasopressin release.