The effect of neuropeptide Y (NPY) on the coronary circulation of the closed-chest dogs (n = 7) was studied. The left circumflex artery was cannulated and perfused with arterial blood withdrawn from the femoral artery. The flow was kept constant by a roller pump and it was monitored by an electromagnetic flowmeter. An increase in the perfusion pressure which was characterized by a slow onset and long-lasting effect (more than 10 min) was found in each dog after NPY. There were no significant changes in the arterial blood pressure, central venous pressure and heart rate. The peak rise was observed at about 1 min; from 108 +/- 9 mmHg to 144 +/- 13 mmHg (mean +/- SE) (p less than 0.01). This increase in the perfusion pressure resulted from vasoconstriction distal to the cannula. When the doses of NPY was changed, a dose-response relation was found (n = 4). Phentolamine did not inhibit the vasoconstrictor effect of NPY (n = 4). The endogeneous substance NPY might be engaged in the regulation of myocardial perfusion and can be a candidate responsible for coronary spasm.