The direct and reflex-mediated components of the cardiovascular response to administration of neuro-peptide Y (NPY) in intact conscious rabbits were determined by studies with cardiac beta adrenoceptor and vagal blockade, and during total autonomic blockade. Cardiac pacing was used to prevent bradycardia, and sinoaortic denervation (SAD) was used to remove afferent baroreflex input. In control animals, NPY (10 micrograms/kg bolus i.v.) caused arterial pressure to increase from 77.4 +/- 1.5 mm Hg (mean +/- SEM) to a maximum of 91.4 +/- 1.6 mm Hg (p less than 0.05). This pressor response was independent of autonomic effectors but was buffered by arterial baroreflexes. The fall in heart rate (HR) from 281 +/- 14 to 252 +/- 18 beats/min (p less than 0.05) was mediated in part through baroreceptor-dependent changes in cardiac autonomic efferent activity, but was in part independent of autonomic neural mechanisms. Peak left ventricular (LV)dP/dt fell from 5,551 +/- 342 to 4,182 +/- 394 mm Hg/s (p less than 0.05) following NPY in control rabbits. This reduction was maintained during pacing and following SAD, and was caused partly by a withdrawal of cardiac beta-adrenergic tone and partly through a non-beta-mediated myocardial depression. Small changes in cardiac output (CO) and in LV end-diastolic pressure (LVEDP) after NPY were secondary to bradycardia. Total autonomic blockade did not impair the NPY-induced rise in total peripheral resistance (TPR), suggesting a direct vasoconstrictor action that was independent of neural mechanisms.