The effects of coronary artery reperfusion at 1 and 3 h after occlusion on infarct size (IS) in the conscious dog were compared with a second group of dogs that were not reperfused (24 h occlusion). Infarct size was calculated from creatine kinase (CK) appearing in blood samples (IS_s) and myocardial CK depletion (IS_m), and determined from gross and histological inspection of the pathological tissue (IS_p). Under both conditions, IS_m correlated well with IS_p. In dogs with 24-h coronary occlusions, IS_s correlated well with IS_m (IS_s = 14.26 + 1.18 × IS_m, r = 0.92). In reperfused dogs, the relationship remained linear but was altered (IS_s = 15.33 + 2.07 × IS_m, r = 0.89). The slope was significantly greater, P <0.05, than that observed for dogs that were not reperfused, suggesting that more CK appeared in serum per gram of infarct. Similarly, significantly different relationships were observed in the reperfused and nonreperfused dogs, when IS_s was compared with IS_p. Moreover, the configuration of the serial blood CK curve was changed significantly by reperfusion. In dogs with a 24-h occlusion, CK rose gradually to a peak at 11.4±0.5 h. In dogs reperfused at 3 h, CK rose sharply at 3 h and reached a peak at 6.8±0.5 h, significantly earlier (P <0.01) than occurred in dogs reperfused at 1 h, i.e., when the peak occurred at 4.2±0.4 h. The rapid appearance of CK in blood after reperfusion at 1 and 3 h suggested a washout phenomena. Thus, reperfusion alters the shape of the serial blood CK curve and results in a different linear relationship between calculated and measured infarct size, resulting in greater recovery of CK in blood per unit of infarcted myocardium.