During a 7-year period, a 15-year-old boy experienced recurrent attacks that clinically and pathologically resembled Reye's syndrome. The attacks were precipitated by prolonged exercise, fasting or infections. An extensive investigation failed to identify a toxic cause or specific metabolic disorder. Low 14CO2 production after in vitro incubation of the patient's liver with 14C-labeled palmitate, citrate and glutamine suggested a defect in the Krebs cycle or the oxidative phosphorylation pathway. This error may be responsible for the recurrent Reye-like syndrome attacks.