The effects of a high-fat diet on ketonemia and other plasma parameters of gluconeogenesis and ketogenesis were studied in rabbits during feeding, during a 4-day fast, and again during refeeding. Arterial plasma glucose, lactate, total aminoacids, ketone bodies, insulin and glucagon were measured daily. In the fed state, the high-fat diet induced an increase in plasma NEFA and ketone bodies and a decrease in alaninemia. The most striking effect of the high-fat diet, compared with the normal low-fat diet was the twofold increase of ketonemia during fasting, even though the difference in NEFA level after both diets was only 19%. This effect was maintained throughout the fasting period. The high-fat diet also induced higher glycemia and lower alaninemia during further fasting. Insulinemia sharply decreased to a very low value from the beginning of fasting, but the high-fat diet did not have any particular effect. Glucagonemia was not different in the fed state than in fasting, whatever preceding diet was given. Therefore, lipid content of the diet prior to fasting introduced important and persistent modifications in the triglycerides and glucose metabolism during fasting.