Following ventromedial hypothalamic lesions, food intake increased from 60 to slightly more than 77 kcal/day during the first 6 days. Body weight increased and sympathetic activity, as measured by the electrical firing rate of efferent nerves to interscapular brown adipose tissue, decreased significantly. During a 6-day period of intragastric overfeeding in which animals with hypothalamic lesions received 60 kcal for the first day and 80 kcal for the remaining 5 days, the VMH-lesioned animals gained significantly more weight than the intact, sham-lesioned controls. This difference in weight gain was paralleled by the increased weight of liver and white adipose tissue. The lesioned animals showed a highly significant reduction in sympathetic activity compared to the normal or slightly increased values observed in the sham-lesioned animals. These studies are consistent with the hypothesis that food-induced increases in sympathetic activity are modulated by the ventromedial hypothalamus.