Clinical records and histologic specimens of liver from 42 patients with hepatitis after exposures to halothane showed clinical and pathologic features helpful in differentiating hepatitis from other causes of jaundice in the postoperative period. Fever and jaundice were temporally related to operation. Peripheral eosinophilia was common, and splenomegaly was unusual. Light-microscopic examination showed the hallmarks of viral hepatitis. Although steatosis, granuloma formation, and eosinophils in the inflammatory exudate were noted frequently, these additional findings were not diagnostic. Sera of six patients examined contained antimitochondrial antibodies, and electron microscopic studies in two cases showed mitochondrial abnormalities not found in viral hepatitis. Because of the clinical features and some of the histologic findings the lesion was considered a hypersensitivity reaction differing from shock. The presence of circulating antibodies supports this finding. The majority of patients developed hepatitis after repeated exposure to the anesthetic agent. None had evidence of preexisting liver disease. The recognition of the mild or early stages of the hepatitic reaction is important to prevent subsequent administration of halothane.