Acute hypoxia increases heart rate (HR) and cardiac output (Qt) at a given oxygen consumption (V̇O2) during submaximal exercise. It is widely believed that the underlying mechanism involves increased sympathetic activation and circulating catecholamines acting on cardiac β receptors. Recent evidence indicating a continued role for parasympathetic modulation of HR during moderate exercise suggests that increased parasympathetic withdrawal plays a part in the increase in HR and Qt during hypoxic exercise. To test this, we separately blocked the β-sympathetic and parasympathetic arms of the autonomic nervous system (ANS) in six healthy subjects (five male, one female; mean ±s.e.m. age = 31.7 ± 1.6 years, normoxic maximal V̇O2 (V̇O2,max) = 3.1 ± 0.3 l min−1) during exercise in conditions of normoxia and acute hypoxia (inspired oxygen fraction = 0.125) to V̇O2,max. Data were collected on different days under the following conditions: (1)control, (2) after 8.0 mg propranolol I.V. and (3) after 0.8 mg glycopyrrolate I.V. Qt was measured using open-circuit acetylene uptake. Hypoxia increased venous [adrenaline] and [noradrenaline] but not [dopamine] at a given V̇O2 (P < 0.05, P < 0.01 and P= 0.2, respectively). HR/V̇O2 and Qt/V̇O2 increased during hypoxia in all three conditions (P < 0.05). Unexpectedly, the effects of hypoxia on HR and Qt were not significantly different from control with either β-sympathetic or parasympathetic inhibition. These data suggest that although acute exposure to hypoxia increases circulating [catecholamines], the effects of hypoxia on HR and Qt do not necessarily require intact cardiac muscarinic and β receptors. It may be that cardiac α receptors play a primary role in elevating HR and Qt during hypoxic exercise, or perhaps offer an alternative mechanism when other ANS pathways are blocked.