Total and MB serum creatine phosphokinase (CPK) activity levels were measured serially in 30 patients treated with direct current electrical countershock, 17 patients with acute myocardial infarction and 25 normal subjects. In addition, serial determinations of total and MB CPK in serum were performed in 11 closed chest anesthetized dogs subjected to 10 repetitive countershocks at 15 second intervals with a delivered energy of 240 joules per countershock. Less than 4 milli-international units (mlU)/ml of MB CPK was found in the serum of normal subjects. Patients with myocardial infarction whose elevated total CPK levels were comparable with those of patients treated with cardioversion had a substantial rise in MB CPK activity, with peak values averaging 39 ± 6 mlU/ml (mean ± standard error). Fifteen of the 30 patients treated with countershock had elevated total CPK activity that peaked within 4 hours. In this group, MM CPK elevations accounted for the overall rise in CPK activity. In two patients, modest elevations of MB CPK (11 and 13 mlU/ml, respectively) were observed after cardioversion. In all 11 dogs total CPK increased after countershock, peaking to 1,888 ± 410 mlU/ml within 6 hours. Six dogs had increased MB CPK activity (52 ± 6 mlU/ml) and myocardial necrosis demonstrable histologically 4 days later. The results indicate that (1) myocardial damage in dogs produced by intense, repetitive countershock is associated with increased serum MB CPK; and (2) countershock as conventionally used in patients does not generally produce myocardial damage and serum MB CPK elevation. Although release of MB CPK into serum occasionally occurs after countershock, perhaps reflecting myocardial damage, the elevations appear to be modest. Thus, electrical countershock does not obscure the diagnosis of myocardial infarction or impair quantitative assessment of the extent of myocardial damage based on analysis of serum MB CPK activity.