Extreme elevation of the serum aspartate aminotransferase level typically suggests acute hepatocellular necrosis and may militate against the diagnosis of chronic active hepatitis. However, we found that 26 of 160 patients (16%) with chronic active hepatitis had aminotransferase elevations of more than 1,000 IU/liter. These patients were younger and more often jaundiced than the others, but they exhibited signs of chronic liver disease as often. In only 2 of 26 patients with extreme aminotransferase abnormality were features of chronic disease absent. Patients with extreme enzyme elevation had histologic findings of confluent necrosis (P greater than 0.005) and features associated with acute viral infection (P greater than 0.005) more often than others, but they as often had cirrhosis on biopsy specimens. Virologic markers did not distinguish the patients or correlate with viral features in liver tissue. Corticosteroids improved immediate survival (P greater than 0.005) and the likelihood of remission (P greater than 0.005). Although chronic active hepatitis may present with extreme aminotransferase elevation and histologic features associated with acute viral infection, ancillary features of chronic disease facilitate the correct diagnosis and the initiation of appropriate therapy.