The skate is an extant representative of the first vertebrate group with a coronary circulation, the elasmobranch fish. Histochemical studies have revealed that skate coronary arteries are innervated by adrenergic nerves as well as by nerves showing neuropeptide Y (NPY)-like immunoreactivity. This study investigates the effect of NPY in the coronary system of an elasmobranch fish, a vertebrate that first evolved 450 million years before mammals and the mammalian coronary circulation. The responses of vascular ring preparations of the coronary artery from the longnose skate (Raja rhina) were measured using isometric force transducers. The main effect of NPY was a potentiation of the amplitude of the norepinephrine-induced contraction, leaving the pD2 value (-log 50% effective concentration) for norepinephrine unaffected. NPY per se occasionally contracted the coronary rings in higher concentrations. The potentiation response may not involve the endothelium and was abolished by pretreatment with tetrodotoxin. We conclude from this study that NPY potentiates norepinephrine-induced contraction in skate coronary artery via an indirect pathway.