Abstract Stress hyperglycemia occurs in normal and chronically hypoxemic dogs when PaO 2's are acutely lowered below 30 torr. Several factors are thought to contribute to the rise in blood glucose. The initial fall in PaO 2 activates the sympathetic nervous system, stimulating alpha and beta adrenergic receptors. Because of reduced beta receptor function, alpha receptor effects predominate, promoting glucagon and inhibiting insulin release. The changes in pancreatic hormones in conjunction with the direct effects of hypoxemia and alpha receptor stimulation increase hepatic glycogenolysis. Meanwhile, glucose clearance is decreased because of elevated circulating levels of catecholamines and low insulin concentrations. This combination of events plays a major role in the development of hyperglycemia. Since high blood glucose levels seems to protect the brain and other vital organs at low oxygen tensions, the development of hyperglycemia may represent an important protective mechanism in severely hypoxemic animals, including humans.