In the dog, shock, regardless of its etiology, resulted in increased oxidative utilization of substrates which form lactate and pyruvate as intermediary metabolites. A concomitant decrease in free fatty acid [FFA] oxidation is implied as the oxidative pathway of the latter does not involve the lactate-pyruvate step. To test this hypothesis, FFA metabolism was investigated by infusing 14C labeled fatty acid in 12 normal dogs, in 9 animals in shock due to controlled cardiac tamponade and in 6 animals with [Escherichia coli] endotoxin shock. The shock state was characterized by a significant (P < 0.05) decrease both in arterial fatty acid concentration and in FFA turnover. Both the rate of FFA oxidation and the percentage of the total CO2 derived from free fatty acid oxidation were significantly (P < 0.05) diminished. Urea production rates were higher in shock, and the calculated maximum contribution of protein oxidation to total CO2 production rose from 23% in the control animals to 50% in the test groups.