Luminal perfusion of 5.0 mM indole (0.5 ml/min) in small intestine lowered hepatic adenylate energy charge [(ATP + ADP/2)/(ATP + ADP + AMP)] from 0.85 to 0.80. 2. Liver perfusion of indole (0.5, 5.0 mM) also lowered adenylate energy charge. 3. In liver perfusion experiments, both ketone body ratio (beta-hydroxybutyrate/acetoacetate) and oxygen concentration of the effluent fluid were decreased by infusion of 0.5 mM indole, but they were increased by 5.0 mM indole. 4. In the isolated liver mitochondria system, indole uncoupled oxidative phosphorylation at lower concentrations than 2.0 mM. However, higher concentrations of indole inhibited the electron transport system.