Hypotension with ventricular pacing has generally been attributed to loss of atrial transport, but it has been suggested that atrial vasodepressor reflexes may play a role. To study this, constant rate atrial and ventricular pacing was performed in 20 supine patients 24 to 36 hours after surgical coronary artery bypass or aortic valve replacement. The pulmonary capillary wedge tracing was examined for the presence or absence of cannon A waves during ventricular pacing in each patient. Thirteen patients had cannon A waves (group I) and seven did not (group II). Ten of the 13 patients with cannon A waves had ventriculoatrial conduction compared with only 2 of 7 patients without cannon A waves. There was a nonsignificant trend toward an association between cannon A waves and ventriculoatrial conduction (p = 0.1). Stroke volume index decreased in both groups when patients were changed from atrial to ventricular pacing. In the patients with cannon A waves, stroke volume index decreased from 31.2 to 26.3 cc/min per m2 (p < 0.001) and from 31.2 to 25.0 cc/min per m2 (p < 0.001) in those without cannon A waves (group I versus group II, p = NS). However, mean systemic blood pressure decreased only in patients with cannon A waves (99.4 to 85.9 mm Hg [p < 0.001] versus 101.8 to 100.9 mm Hg [p = NS]) in those without cannon A waves (group I versus group II, p < 0.001). Hypotension in patients with cannon A waves was caused by inhibition of the normal reflex increase in systemic vascular resistance. In these patients, systemic vascular resistance increased only 5%, whereas in those without cannon A waves it increased 23% (group I versus group II, p < 0.002). It is concluded that hypotension with ventricular pacing is primarily due to a vasodepressor reflex initiated by left atrial cannon A waves. Although ventricular pacing generally causes a decrease in stroke volume due to loss of normal atrial transport, the induction of hypotension requires the presence of left atrial cannon A waves that inhibit normal vascular reflexes. These hemodynamic consequences of ventricular pacing in susceptible patients may be prevented by maintaining atrial synchrony with atrial or dual chamber pacing.