We have used multiple isotope infusions to study the integrated response of glucose, fat, and protein metabolism to combined alpha + beta-adrenergic blockade in conscious, unstressed, fasting (15 h) dogs. The response to the blocking agents was evaluated both with and without control of the glucoregulatory hormones. The hormones were controlled at the basal level by infusions of somatostatin and metyrapone to block their secretion, and by the infusion of insulin, glucagon, growth hormone, and cortisol at physiological rates. We found that adrenergic blockade markedly inhibited lipolysis, as reflected by falls in glycerol and plasma FFA appearance. The decrease in fat mobilization after blockade resulted in a proportionate shift from fat as an energy substrate toward carbohydrate. Glucose production and oxidation were both enhanced after blockade. The source of the increased glucose production was presumably hepatic glycogen because urea production was presumably hepatic glycogen because urea production was unaffected and glycerol uptake was decreased. These results are consistent with the interpretation that basal adrenergic activity plays an important role in the mobilization of fat in fasting dogs. A secondary consequence of that action is apparently a diminution of glucose production and oxidation, although the mechanism responsible for the latter response is not clear.