To determine whether the extent of infarction can be estimated enzymatically soon after reperfusion, the rate of increase of creatine kinase (CK) activity in plasma early after coronary recanalization was compared with infarct size in 18 dogs and 10 patients. In dogs, reperfusion was initiated 2 to 4 hours after coronary occlusion. CK activity was measured in serial plasma samples and infarct size was assessed histochemically at 24 hours. A substantial and consistent fraction of the total CK appearing in plasma over 24 hours (cumulative CK) appeared in plasma soon after reperfusion, i.e., 21 ± 2% (SE) within 30 minutes and 38 ± 3% within 1 hour. The rate of increase of plasma CK activity correlated closely with infarct size when CK release was measured during the first 30 minutes (r = 0.92) or 60 minutes (r = 0.92) after reperfusion (n = 18). Similarly, in patients the rate of increase of CK activity measured within 2.5 hours of the time of reperfusion was closely related to infarct size delineated by positron emission tomography 1 to 2 weeks later (r = 0.93). Thus the rate of appearance of CK in plasma early after reperfusion reflects the extent of irreversible injury ultimately sustained and provides a criterion likely to be useful for prospective identification of patients at high risk after coronary recanalization.