γ-glutamyl transpeptidase, an enzyme found by histochemical means to be located near the luminal border of endothelial cells, is shown to be elevated in the sera of patients with epilepsy. Elevations previously described have been confined to sera from patients with diseases of the liver and biliary system and from patients who have had myocardial infarctions. The increased activity in patients with epilepsy is apparently not the result of hepatotoxicity from drug administration. Elevated activity is not observed in cerebrospinal fluid of patients with epilepsy. Serum γ-glutamyl transpeptidase is also elevated following neurosurgery in patients with intracranial tumors. Similarities following neurosurgery in the patterns of this enzyme, 5′-nucleotidase, and alkaline phosphatase to those seen following myocardial infarction are described.