Neuropeptide Y (NPY) has prominent cardiovascular effects in mammals and sharks, but no such effect has previously been demonstrated in any teleost fish. In the Atlantic cod, we found that cod NPY (10¹⁰-10⁶ M) relaxed celiac arteries precontracted with epinephrine, and weak contractions were elicited in intestinal ring preparations. A few NPY-immunoreactive nerve fibers were present along small gut arteries. The results suggest that cod NPY produces vasorelaxation both by a direct action on smooth muscle and by release of prostaglandins, but with no involvement of nitric oxide, leukotrienes, or endothelium-derived relaxing factors. An additional indirect effect involving another neurotransmitter may occur. Cod NPY (10⁷ M) and human NPY (10⁷ M) had identical effects on the vessels. Small differences only in the effects of porcine [Leu³¹,Pro³⁴]NPY, NPY-(13-36), and cod NPY suggest the presence of a Y₁ subfamily receptor, similar to the zebrafish Ya receptor. A physiological role for NPY in teleost vasculature is concluded, but surprisingly the effect, a vasodilation, is opposite to that in mammals and is mediated by prostaglandins.