Central catecholaminergic neurons are involved in cardiovascular regulation. Neuropeptide Y (NPY) coexists with adrenaline and noradrenaline in the rat brain, and interactions among these substances have been studied. The purpose of this study was to investigate the possible role of NPY in central cardiovascular control. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure was monitored intra-arterially. Intramedullary microinjection (60 nl) of NPY (0, 46.5 fmol, 465 fmol, 1.5 pmol, and 4.65 pmol) was made into the nucleus tractus solitarii (NTS), into the area postrema, and into the C1 area in the rostroventrolateral medulla. Injection site was identified by L-glutamate administration and confirmed histologically. Unilateral injection of NPY into the NTS produced a prominent dose-related decrease in heart rate and systolic and diastolic blood pressure (-106±8 beats/min, -56±2 mm Hg, and -33±2 mm Hg, respectively after 4.65 pmol NPY, n=7, p<0.001). Maximal changes occurred at 30 seconds and recovered in 10 minutes for blood pressure and 20 minutes for heart rate. Injection into the area postrema produced an initial increase in heart rate and mean blood pressure (+23 ±2 beats/min and +18 ±2 mm Hg) followed by a prolonged decrease in heart rate and mean blood pressure (-14±4 beats/min and -15±2 nun Hg, respectively, n=7, /?<0.01). However, injection of NPY into the Cl area produced a dose-related increase in blood pressure and a decrease in heart rate (+17±1 nun Hg and -23±8 beats/min, n=6, p<0.01). To test the specific effect of NPY, rabbit anti-NPY antiserum was used. Prior administration of the antiserum inhibited the effects of subsequent administration of NPY, whereas inactivated antiserum was not able to prevent these effects. These studies demonstrate that NPY has powerful cardiovascular effects in the NTS, area postrema, and Cl area of the medulla oblongata of the rat. This finding suggests that NPY may be important in cardiovascular regulation.