Feeding medium-chain triglycerides (MCT) is reported to result in less weight gain as fat than feeding long-chain triglycerides (LCT). In this experiment, fatty acid metabolism was studied in hepatocytes isolated from rats fed high fat diets containing MCT (70.9% of total energy), LCT (72.3% total energy) or a low fat (LF) (10.8% total energy). In the MCT group, hepatocyte utilization of [1-14C]oleate or [1-14C]octanoate, unlabeled ketone body (KB) production and lipogenesis (LG) were greater than in the other groups. Esterified products (EST) from both fatty acids were greater in the MCT groups, and 5-tetradecycloxy-2-furoic acid, an effective inhibitor of LG, did not abolish this. Lactate/pyruvate increased EST from octanoate and total LG but had little effect on octanoate oxidation. These data suggest that the capacity of medium-chain fatty acid esterification is adaptable to MCT content of the diet and may help regulate their metabolic fate. Despite high rates of KB production in the MCT group, the NADH-NAD ratio was not elevated. Rapid lipogenesis may contribute to the utilization of the excess energy equivalents formed. High LG and EST in the presence of a glycerol precursor may limit the usefulness of MCT in dietetic products for weight control. The animal fed an MCT diet is unusual in that the antithetical pathways of fatty acid catabolism and anabolism are being carried out simultaneously and at rapid rates. The lesser food efficiency of MCT may be related to the energy losses necessarily associated with cycling between these processes.(ABSTRACT TRUNCATED AT 250 WORDS)