The effect of hypoxia (SpO2 80%) on the arteriovenous production of endothelin-1 (ET) in the forearm was investigated in six healthy volunteers. In eight other subjects the local vascular effects of a low physiologic dose of intra-arterially administered ET (0.5 pg/kg/min) was studied during normoxia. Forearm blood flow (FBF) was measured by venous occlusion plethysmography, and arterial and venous plasma concentrations of ET were measured. FBF was not significantly influenced during hypoxia. After 15 min of hypoxia the arterial plasma level of ET increased from 2.5 +/- 0.1 to 3.3 +/- 0.3 ng/L (p < 0.05), whereas the venous plasma level remained unchanged. Intra-arterial infusion of ET increased the arterial plasma level of ET in the forearm from 2.2 +/- 0.3 to 4.9 +/- 0.4 ng/L. This increase in ET concentration did not influence FBF. It is concluded that hypoxia is a stimulus for ET release from the pulmonary vascular bed and that the resulting increase arterial plasma ET level does not influence peripheral vascular tone.