The effect of hyperbaric oxygen (HBO) on infarct size associated with myocardial infarction remains uncertain. Accordingly, the present study was performed in 46 conscious dogs with experimental infarction to determine the effect of HBO on enzymatic estimates of infarct size. Since HBO may affect plasma creatine kinase (CK) release or disappearance, parameters used to calculate enzymatic estimates of infarct size from plasma CK, we assessed infarct size by directly measuring myocardial CK depletion. Twenty-three animals were given HBO (2 atm of pressure) for 3 h immediately after coronary occlusion and results of infarct size compared to those in 23 dogs with occlusion who remained in room air. In 10 other animals CK release was measured after coronary occlusion in 5 controls and compared to 5 treated. In 5 normal animals the CK disappearance rate of purified canine CK was determined before and after HBO. Infarct size was determined 24 h after coronary occlusion and in the treated animals averaged 25.4 +/- 1.3% of LV (mean +/- SEM), and being similar to controls (26.7 +/- 1.4, P greater than 0.25). The plasma CK disappearance rate before and after HBO was the same being 0.0072 +/- 0.0022 (min-1) and 0.0073 +/- 0.0021, respectively. Total CK released into the plasma was also the same in treated and controls (2232 +/- 210 IU and 2011 +/- 232), as was the ratio of CK released to that depleted from the myocardium (0.15 +/- 2% vs 0.15 +/- 3%). Our results indicate: (1) HBO does not reduce infarct size produced experimentally in the conscious dog; (2) HBO does not affect CK release or disappearance; and (3) estimates of infarct size by plasma CK remain valid despite administration of HBO.