In acute myocardial infarction the effect of oxygen administration in modifying infarct size is uncertain. To evaluate this as well as the effects of moderate hypocarbia, four groups of anesthetized dogs were studied experimentally for 2 hours after coronary branch ligation: group I (controls; room air, normal blood gases): group IIA (FIo2 50%, normal Paco2); group IIB (FIo2 50%, low Paco2); and group IIC (50% oxygen given after ligation, normal Paco2). In addition to hemodynamics, the effect of differing blood gas patterns on hemoglobin-oxygen affinity (P50) and ischemic alterations of myocardial electrolyte and water content were evaluated. Hemodynamic changes among the four groups included decreases in LV ejection fraction and cardiac output. The latter was more pronounced in the oxygen treated groups with proportionately greater increases in systemic resistance. P50 increased in all groups, indicating decreased hemoglobin-oxygen affinity; in group IIC this increase was significantly greater than in group I. In all groups an analysis of central and border areas of myocardial ischemia showed loss of potassium and gain of sodium and water, but no beneficial effect on this result by oxygen administration pre or post ligation could be demonstrated. On the contrary, among those dogs administered oxygen the ischemic changes appeared more pronounced than in the control group. Moderate hypocarbia did not modify the myocardial electrolyte and water change. The results of this study do not support the hypothesis that oxygen administration can favorably modify the myocardial changes of ischemia, at least early in the course of myocardial infarction.