In order to investigate the influence of the endothelium on hypoxia-induced vasospasms we examined vascular tone after reduction of the oxygen supply, dependent on endothelial function. Therefore, after ligation of all side branches, vessel segments of porcine or human right coronary arteries or of rabbit abdominal aorta, prepared either with or without endothelium, were cannulated, perfused with Tyrode's solution and arranged in a serial manner (system I: endothelium-denuded vessel followed by a normal segment; system II: normal vessel followed by an endothelium-denuded segment). The pressure gradient over each segment was continuously measured as a function of vessel radius. After 2 h equilibration the oxygen concentration in the perfusion and superfusion solutions was lowered (reduction from 'control' = 95% O2/5% CO2 to 'hypoxia' = 95% N2/5% CO2) leading to a marked long-lasting vasoconstriction in those endothelium-denuded vessel segments which were mounted distal to a normal vessel with an intact endothelium, whereas the other vessels did not change their tone. This hypoxic contraction could be inhibited by pretreatment with either 1 mumol l-1 dexamethasone or quinacrine or indomethacine. From these results it is concluded that endothelium releases a vasoconstricting factor (EDCF) under hypoxic conditions probably dependent on phospholipase A2 and cyclooxygenase. This EDCF may be of pathophysiological importance by inducing or aggravating hypoxic vasospasms.