The vascular effects of 15-hydroperoxyeicosatetraenoic acid (15-HPETE) and 15-hydroxyeicosatetraenoic acid (15-HETE) were investigated on isolated helical strips of canine cerebral and coronary arteries. 15-HPETE caused strong concentration-related contraction of cerebral arteries under resting tension. After contraction with prostaglandin F2 alpha (PGF2 alpha), 15-HPETE caused marked relaxation of coronary arteries. The effects of 15-HETE on isolated canine arteries were similar to those of 15-HPETE. The relaxation of coronary arteries caused by both 15-HPETE and 15-HETE was completely inhibited in the presence of aspirin, but not in the presence of tranylcypromine. Preincubation of coronary and cerebral arterial strips with 15-HPETE or 15-HETE resulted in suppression of the production of 6-keto-PGF1 alpha from exogenously added arachidonic acid; and 15-HPETE, but not 15-HETE, enhanced the production of HETE(s) significantly. Aspirin blocked 15-HPETE induced HETE(s) production in coronary arteries. On cerebral angiography, strong contraction of intracranial arteries was observed after intracisternal injection of 15-HPETE. On the other hand, 15-HETE had little effect on intracranial arteries in vivo. The mechanism of the vascular effects of 15-HPETE and 15-HETE will be discussed.