We recently demonstrated that cortical microsomes from spontaneously hypertensive rats metabolize arachidonic acid via cytochrome P450 to omega- and omega-1 hydroxylated compounds, 19- and 20-hydroxyeicosatetraenoic acids (HETE). The vascular activities of 20-HETE and the two isomers of 19-HETE were examined in rat aortic rings. The HETEs produced concentration-dependent contractions of the aortic rings. The contraction elicited by 20-HETE was abolished partially by removal of endothelium and was inhibited completely by treatment with indomethacin and reversed to a relaxation response by treatment with the endoperoxide and thromboxane receptor antagonist SQ 29548. These data suggest that the vascular effects of 20-HETE depend on subsequent metabolism by cyclooxygenase.