1. The mechanisms of release of pancreatic glucagon, insulin and pancreatic polypeptide (PP) in response to hypoxia and to 2-deoxyglucose have been investigated in conscious calves 3-5 weeks after birth. 2. A single injection of 2-deoxyglucose (200 mg/kg I.V.) produced an abrupt rise in the concentrations of pancreatic glucagon, insulin and PP in the arterial plasma. The changes in plasma insulin and PP concentration were unaffected by prior section of the splanchnic nerves but were effectively abolished by atropine (0-2 mg/kg I.V.). The rise in plasma pancreatic glucagon concentration was prevented in calves with cut splanchnic nerves that were given atropine but neither procedure alone suppressed the response. 3. 2-deoxyglucose also caused a substantial increase in the output of glucocorticoids from the right adrenal gland together with a pronounced rise in adrenal blood flow. There was also a small but significant increase in catecholamine output from the adrenal medullae in these animals. 4. Intense hypoxia caused a pronounced increase in the concentration of PP in the arterial plasma. This was found to resemble the glucagon response to intense hypoxia in that it persisted in animals with cut splanchnic nerves that were given atropine. Less intense hypoxia caused a rise in plasma pancreatic glucagon concentration (but not PP) that was abolished by section of the splanchnic nerves. The changes in plasma insulin concentration in these experiments were consistent with the conclusion that they were secondary to changes in plasma glucose concentration. 5. It is concluded that pancreatic endocrine responses to both moderate hypoxia and 2-deoxyglucose are mediated by the autonomic innervation.