We studied plasma glucagon (IRG) in hypoxia because other stressful states stimulate glucagon release. Two groups of paired experiments were performed in 12 puppies. In Group I, 8%02: 92%N2 ventilation (Pa02 20-30 torr) for 45-min. produced a rise in plasma IRG (mean change +100.5 pg/ml) and glucose(+223.7mg/dl) but no change in insulin (IRI) (-.3 μ/ml). However, when Group I was air ventilated (Pa02 >70 torr) and given 45-min. glucose infusions producing hyperglycemia of similar degree (+196 mg/dl), plasma IRG was unchanged (-7.8 pg/ml) while IRI (+32.8 μ/ml) rose. The IRG and IRI responses with 45-min. of hypoxia were different from those during a comparable period of air (p<.03). Because B adrenergic receptor stimulation mediates glucagon release in stressed dogs, its contribution to the IRG rise in hypoxia was examined by giving Group II the β adrenergic blocker, propranolol. Despite β blockade, 8%02: 92%N2 ventilation caused a rise in plasma IRG (+394 pg/ml) and glucose (+71 mg/dl), but IRI was unchanged (+ .8 μ/ml). With propranolol and air ventilation there were no significant changes in plasma IRG(+14.7pg/ml) glucose (+9 mg/dl) or IRI (+6.7μuml/). These data suggest that a) glucagon release is caused by acute 02 deficiency, but b) without B adrenergic receptor mediation. Since hepatic glycogenolysis, the primary glucose source in hypoxia, is stimulated by glucagon and retarded by insulin, we propose that increased glucagon and low insulin levels promote glucose mobilization and hyperglycemia at low 02 tensions.