Animal studies have demonstrated an important role for the sympathetic nervous system in food-induced increases in energy expenditure. Despite studies in man showing a rise in plasma norepinephrine after a meal, no relationship has previously been demonstrated between the increment in plasma norepinephrine and the increase in energy expenditure. Because changes in plasma norepinephrine may not always accurately reflect alterations in sympathetic nervous system activity, we investigated the effects of an 800-kcal high-carbohydrate meal on both plasma norepinephrine kinetics and energy expenditure as well as their relationship to each other. A post-cibum increase in both energy expenditure (0.18 +/- 0.09 kcal/min, P less than 0.001) and plasma norepinephrine concentration (44 +/- 39 pg/ml, P less than 0.05) was noted but again no relationship between the two parameters was found. In contrast, the increment in norepinephrine appearance rate after the meal (0.11 +/- 0.09 microgram/min, P less than 0.001) was significantly correlated to the increment in energy expenditure (r = 0.57, n = 20, P less than 0.01). No change was noted in norepinephrine clearance rate after the meal. It is concluded that sympathetic nervous system induced increases in energy expenditure may account for at least part of the thermogenesis that occurs after a high-carbohydrate meal. It is postulated that individual variability in this sympathetic nervous system induced component of the thermic effect of feeding may account for some of the differences in energy expenditure noted between obese or elderly subjects and normal weight young controls after a meal.