The prognostic effect of the peak level of serum creatine kinase (CK) and aspartate transaminase (AST), estimated daily for 3-5 days after acute myocardial infarction, was studied in 560 patients who survived the first day in hospital. In a subgroup of 54 patients, peak enzyme levels correlated well with the cumulated CK release (r = 0.90 with peak CK, r = 0.74 with peak AST), thus reflecting the extent of myocardial necrosis. Total mortality within a year after infarction was not significantly different in the lower three quintiles of peak serum enzyme level, but increased from 15.5% to 27.9% (p lt; 0.001) when peak CK level exceeded eight times the upper limit of normal (8 X N) and from 13.1% to 34.8% (p lt; 0.001) when peak AST level exceeded five times the upper limit of normal (5 X N). The effect of high enzyme levels was more marked in patients with a prior history of myocardial infarction; mortality increased from 14.7% for first infarctions to 18.2% for recurrent infarctions, with peak CK < 8 X N, and from 27.0% for first infarctions to 38.0% for recurrent infarctions with peak CK > 8 X N. Early mortality was more significantly affected (p lt; 0.0001) than late mortality (p lt; 0.05). In hospital survivors, late deaths from cardiac decompensation were three times (p lt; 0.05) more frequent in the high enzyme group as in the low enzyme group, but the number of sudden deaths was unaffected. These findings have important implications for studies of reduction of myocardial infarct size.