The present study was undertaken to determine the effects of intracoronary administration of the veratrum alkaloid veratridine on coronary blood flow and resistance in conscious, chronically instrumented intact and sinoaortic denervated dogs. Ten dogs were instrumented with a Doppler flow probe on the left anterior descending coronary artery. A chronic catheter was placed in the left circumflex coronary artery and in the aorta and left atrium. A Konigsberg pressure cell was placed in the left ventricle, and pacing leads were attached to the left atrium and ventricle. While heart rate was kept constant, bolus intracoronary injections of veratridine (0.1-0.4 microgram/kg) were administered in the unblocked state after beta 1-receptor blockade, after alpha-receptor blockade, and after cholinergic blockade. In the unblocked state, late diastolic coronary resistance fell by 34.7 +/- 5.0%. The maximum response was achieved at a time when arterial pressure was not significantly different from control. After beta 1-blockade, coronary resistance fell by 29.1 +/- 7.9%. After combined alpha- and beta-blockade, coronary resistance fell by 25.4 +/- 6.5% in response to veratridine. The addition of atropine completely blocked the decrease in coronary resistance, changing it by an average of -0.10 +/- 2.5%. The responses in sinoaortic denervated dogs were similar to those in intact animals. The response was abolished by vagotomy. We conclude that cardiac receptor stimulation causes a reflex decrease in coronary resistance in the awake dog that is completely accountable by a cholinergic mechanism.