Production of ketone bodies, activation of oxygen uptake and production of [14C] carbon dioxide due to fatty acids of various chain lengths were measured in the isolated perfused rat liver. As ketogenic substrates, the fatty acids investigated can be ordered in the following sequence: stearate less than palmitate less than laureate less than decanoate less than miristate less than octanoate. For activation of oxygen consumption, the same sequence is observed. A good linear correlation between the increase in oxygen uptake (delta O2) and production of ketone bodies was found, with a mean delta O2 of 0.66 mol per mol ketone bodies. This is a relatively low value when confronted with the known stoichiometry of beta-oxidation, and may be an indication of complexities in the metabolism of exogenously added fatty acids in the perfused liver.