A percutaneous liver biopsy was obtained from a 9-year-old boy who had elevated serum transaminase levels while receiving aspirin treatment for rheumatic fever. Electron microscopy showed extensive fine-structure changes of the hepatocytes, similar to those induced by hepatotoxic drugs. These included marked dilatation of rough endoplasmic reticulum, proliferation of smooth endoplasmic reticulum, and mitochondrial abnormalities. These ultrastructural changes could be considered evidence that aspirin is hepatotoxic. The morphologic observations reported confirm the need for monitoring patients receiving systemic aspirin treatment transaminase measurements.