Glucose utilization increases markedly in the normal dog during stress induced by the intracerebroventricular (ICV) injection of carbachol. To determine the extent to which insulin, glucagon, and selective (/)-adrenergic activation mediate the increment in glucose metabolic clearance rate (MCR) and glucose production (R_a), we used five groups of normal mongrel dogs: 1) pancreatic clamp (PC; n = 7) with peripheral somatostatin (0.8 µg · kg¹ · min¹) and intraportal replacement of insulin (1,482 ± 84 pmol · kg¹ · min¹) and glucagon (0.65 ng · kg¹ · min¹) infusions; 2) PC plus combined  (phentolamine)- and  (propranolol)-blockade (7 and 5 µg · kg¹ · min¹, respectively; +; n = 5); 3) PC plus -blockade (; n = 6); 4) PC plus -blockade (; n = 5); and 5) a carbachol control group without PC (Con; n = 10). During ICV carbachol stress (0-120 min), catecholamines, ACTH, and cortisol increased in all groups. Baseline insulin and glucagon levels were maintained in all groups except Con, where glucagon rose 33%, and , where insulin increased slightly but significantly. Stress increased (P < 0.05) plasma glucose in Con, PC, and  but decreased it in  and +. The MCR increment was greater (P < 0.05) in  and + than in Con, PC, and . R_a increased (P < 0.05) in all groups but was attenuated in +. Stress-induced lipolysis was abolished in  (P < 0.05). The marked rise in lactate in Con, PC, and  was abolished in + and . We conclude that the stress-induced increase in MCR is largely independent of changes in insulin, markedly augmented by -blockade, and related, at least in part, to inhibition of lipolysis and glycogenolysis, and that R_a is augmented by glucagon and - and -catecholamine effects.