The effects of vagotomy on long-term protein and carbohydrate selection or on short-term food selection following cholecystokinin octapeptide (CCK-8) injections, protein, or carbohydrate premeals and on brain 5-hydroxytryptamine (5HT) and catecholamine metabolism were examined in adult rats. Vagotomy was followed by a reduction in daily protein intake that by 3 wk had fallen to 50% of preoperative levels. A corresponding increase in carbohydrate intake occurred so that total food intake was maintained at approximately 93% of that consumed by the sham-operated controls. These changes in day-to-day macronutrient selection from a choice of high- and low-protein diets were associated with a vagotomy-induced decreased turnover of 5HT in the hypothalamus. In meal consumption studies vagotomy prevented a further reduction in meal size by CCK-8 but did not block decreased consumption of total food or of protein preference of the rats in meals taken subsequent to a protein meal. It was concluded that the vagus nerve plays a role in regulating long-term protein and carbohydrate preferences but not in the relationships among meal-to-meal composition and intake.