Short-chain fatty acids were determined prior to therapy in seven patients with Reye's syndrome. Elevated concentrations of propionate, butyrate, and isobutyrate were found in all patients. Isovalerate concentrations were high in three patients. In view of the fact that the administration of certain short-chain fatty acids to experimental animals results in coma, electroen-cephalographic changes, and fatty accumulation in the viscera, the elevations of short-chain fatty acid concentrations observed in the present study suggest that these fatty acids may play a role in the clinical manifestations of Reye's syndrome.