Objectives. The purpose of this study was to compare the perfusion pressure and rate of return of spontaneous circulation produced by standard advanced cardiac life support with that resulting from advanced cardiac life support with simultaneous aortic occlusion and proximal infusion with oxygenated fluid. Background. Cardiopulmonary resuscitation based solely on external chest compression is unable to achieve return of spontaneous circulation in most patients with cardiac arrest. Adjunctive therapies that enhance myocardial oxygen supply may improve outcomes. Methods. We conducted a prospective, randomized study in mongrel dogs using a fibrillatory model of cardiac arrest with a 20-min arrest time. Dogs were randomized to two groups. Aortic arch and right atrial micromanometers were placed to measure intravascular pressure. Manual external chest compression was used and standardized to an esophageal pulse pressure of 50 mm Hg. Two minutes after initiation of advanced cardiac life support, selective aortic perfusion and oxygenation were initiated in dogs assigned to one group by inflation of an occluding balloon in the descending aorta and infusion of 450 ml of ultrapurified polymerized bovine hemoglobin through a large bore central infusion port. Results. Maximal aortic pressure during standard advanced cardiac life support was 42 +/- 23 (mean +/- SD) versus 69 +/- 28 mm Hg during advanced cardiac life support with selective aortic perfusion and oxygenation. Maximal coronary perfusion pressure during standard therapy was 33 +/- 21 versus 62 +/- 26 mm Hg during combined therapy. Only 2 of 10 dogs receiving standard therapy had return of spontaneous circulation versus 6 of 7 dogs receiving combined therapy. Balloon occlusion alone did not increase perfusion pressure significantly. Conclusions. The use of selective aortic perfusion and oxygenation increases aortic and coronary perfusion pressures during cardiopulmonary resuscitation, resulting in a large increase in the rate of return of spontaneous circulation. This technique may be an effective adjunct to advanced cardiac life support based on any method of external chest compression and may improve the poor prognosis of patients with cardiac arrest.