Lipogenesis and the rate of fatty acid incorporation in vitro were studied in the pericardial and epicardial adipose tissue of the guinea-pig heart and in the liver and two larger adipose depots. Both lipogenesis and the rate of fatty acid incorporation were higher in the cardiac depots than in any of the other tissues studied. The rate of fatty acid incorporation were unaffected by insulin (0.1 U/ml) in the cardiac depots in contrast to all other tissues examined, and lipogenesis was increased by insulin in the cardiac depots, but not in the other adipose depots or liver. High-fat feeding increased the rate of fatty acid incorporation in vitro in all tissues examined, but the rates of lipogenesis were unchanged except in perirenal adipose tissue (decrease) and liver (increase). The data are consistent with the hypothesis that epicardial adipose tissue may act as a local energy store for cardiac muscle and have a protective role against elevated levels of free fatty acid in the coronary circulation.