The effect of epinephrine in dogs with hypokalemia was investigated. Injection of epinephrine, 10 micrograms/kg, induced an elevation of serum creatine kinase (CK) activity and histological changes in myocardium of dogs with hypokalemia. The effect of epinephrine was little in dogs with normokalemia. Heart mitochondrial calcium content was elevated in parallel with the decrease in serum K+ in dogs with hypokalemia. Propranolol, a beta-blocker, did not prevent these changes. Since epinephrine increases coronary blood flow, these alterations cannot be ascribed to a reduction in coronary blood flow. It is likely that calcium overload alone, without ischemia, could develop myocardial injury in dogs with hypokalemia, and that beta-adrenergic action is not involved in this pathogenesis.