Using weanling mice of two different genetic strains we demonstrated a potentiation of the toxic effects of acetaminophen by prior infection with influenza B virus. The C57BL/6N (B6) strain of mice is genetically predisposed to increased toxicity from acetaminophen when the hepatic cytochrome P-450 mixed function oxidase system is preinduced. When B6 animals are pretreated with influenza B virus and an mixed function oxidase system inducing agent before administering acetaminophen, we observed a significant incidence of atypical “fatty” liver pathology on light microscopy similar to the microvesicular steatosis seen in human Reye's syndrome. Electron microscopic changes in the liver of these animals resemble those published to date in human Reye's syndrome.