We have previously shown that rats fed saturated fat prefer a high protein, low carbohydrate diet, whereas animals fed unsaturated fat prefer a low protein, high carbohydrate diet. The purpose of the present study was to determine whether this "saturated fat effect" requires 1) the oxidation of the dietary fat and 2) an intact hepatic vagus nerve. Male Sprague-Dawley rats were vagotomized (hepatic branch) or sham-operated and injected with either mercaptoacetate (fatty acid oxidation inhibitor) or saline. Next, half of each group was given saturated fat (beef tallow) or unsaturated fat (corn oil) by gastric tube. All animals were given a choice between two mixed diets that differed in protein and carbohydrate. Sham-operated rats fed saturated fat ate more of the protein diet than did rats fed unsaturated fat. Vagotomy attenuated the intake of the protein diet in animals fed saturated fat. Mercaptoacetate or vagotomy had no effect on diet selection in rats fed unsaturated fat. These data indicate that the effect of saturated fat on diet selection requires an intact hepatic vagus and may be modulated by fatty acid oxidation. Furthermore, the mechanism for altering diet selection can be induced after a single meal.