Oxygen in high concentration (arterial pO2over 400 mm Hg), administered for 7-10 minutes to six subjects with normal coronary arteries and nine subjects with coronary artery disease caused the following significant changes: The heart rate and cardiac index decreased in both groups. The mean arterial pressure increased in the coronary group. The coronary sinus blood flow fell from 158 ± 11 (mean ± SEM) to 131 ± 13 in the noncoronary and from 151 ± 14 to 138 ± 14 ml/min in the coronary group, due to an increase in coronary resistance. The coronary sinus oxygen tension increased from 19 ± 1 to 22 ± 1 in the noncoronary and from 19 ± 1 to 24 ± 1 mm Hg in the coronary group. The coronary arteriovenous oxygen difference decreased from 13.2 ± 0.6 to 12.5 ± 0.6 ml/100 ml in the coronary group. Left ventricular oxygen consumption fell from 21.5 ± 2.1 to 18.2 ± 2.4 in the noncoronary and from 19.9 ± 2.0 to 16.7 ± 1.7 ml/min in the coronary group. Myocardial lactate extraction increased from 40 ± 9 to 60 ± 4 and from 4 ± 6 to 28 ± 3%, respectively. In four patients with severe coronary artery disease, oxygen breathing reverted myocardial lactate production to extraction. It would appear that oxygen breathing might be beneficial in myocardial ischemia by increasing coronary arterial oxygen tension and reducing myocardial oxygen consumption.