Twenty-one patients aged 4–78 years with influenza A virus–associated acute encephalopathy were studied. Influenza A virus could be detected only in a cerebrospinal fluid (CSF) specimen obtained from 1 of 18 patients, despite the use of a highly sensitive polymerase chain reaction assay. Six patients experienced influenzal encephalopathy during the course of respiratory illness. Five of these patients had hypoprothrombinemia and 4 had increased serum creatinine levels, indicating hepatic and/or renal dysfunction. Fourteen patients experienced postinfluenzal encephalopathy ⩽3 weeks after resolution of acute respiratory symptoms. In 6 patients, focal areas of high signal intensity were visible on T2-weighted magnetic resonance images of the brain. Adenovirus DNA was detected in CSF specimens obtained from 4 (36%) of 11 patients with postinfluenzal encephalopathy. Thus, influenzal encephalopathy is frequently associated with metabolic disorders, whereas postinfluenzal encephalopathy appears to have different possible etiologies.