The short chain fatty acid sodium octanoate was infused into rabbits as an 0.2 M solution over 4 hours, resulting in blood and brain levels of 200 to 700 μmoles per liter. During the infusion, animals exhibited marked hyperventilation, resulting in a mild respiratory alkalosis. Octanoate infusion also resulted in significant hyperammonemia and lactic acidemia. Saline-treated control animals demonstrated no clinical or chemical abnormalities. Several short chain fatty acids, including octanoate, are increased in the plasma of patients with hepatic encephalopathies and Reye syndrome. The present study suggests that short chain fatty acids may be endogenous toxins in these clinical disorders. In particular, the central hyperventilation in these conditions may be due to the neurotoxic effect of short chain fatty acids.