T he present study was designed to test whether there are diurnal changes in the firing rate of sympathetic nerves to brown adipose tissue and whether these diurnal rhythms influenced the response to insulin injected into the suprachiasmatic nucleus or ventromedial hypothalamic nucleus (VMH). Food intake was highest at the beginning of the dark period (1800-2200 hours) and lowest during the daylight hours (0600-1000 and 1200-1600 hours). The basal sympathetic firing rate was highest at noon (1000-1200 hours) when food intake was lowest. At midnight, when food intake was highest, sympathetic firing rate was lowest. Injection of insulin (77, 144, and 288 pmol) into the VMH produced a dose-dependent depression of sympathetic firing rate at each of the four measurement periods (0400-0600 hours, 1000-1200 hours, 1600-1800 hours, and 2200-2400 hours), but the magnitude of the effect was greater at noon than at night. In contrast, insulin injections into the suprachiasmatic nucleus decreased the sympathetic firing rate at noon but produced a significant increase in the sympathetic firing rate at night. These data show that a diurnal rhythm exists for the sympathetic firing rate. The decrease in firing rate in response to insulin when injected into the VMH is in the same direction but varies in magnitude throughout the day, whereas the responsiveness of the suprachiasmatic nucleus to injections of insulin shows a reversal of response in relation to day/night cycles. The highly significant inverse relationship between basal sympathetic firing rate and food intake suggests that sympathetic activity may be part of an important control system for energy balance.