To role of beta-adrenergic and muscarinic cholinergic systems on maximal treadmill exercise performance and systemic O2 transport during hypoxic exercise (PIO2 approximately 70 Torr) was studied in rats acclimatized to hypobaric hypoxia (PIO2 approximately 70 Torr for 3 weeks, A rats) and in non-acclimatized littermates (NA rats). Untreated A rats had lower resting (fH) and maximal heart rate (fHmax) and cardiac output (Q), and higher maximal O2 uptake (VO2max) than NA. The only effect of cholinergic receptor blockade with atropine (Atp) was an increase in pre-exercise fH to comparable levels in A and in NA. beta 1-adrenergic receptor blockade with atenolol (Aten) lowered pre-exercise fH and (fHmax) to comparable values in A and in NA rats. However, since both pre-exercise fH and fHmax were lower in untreated A, the effect of Aten was relatively smaller in A. Aten reduced maximal exercise cardiac output (Qmax) in NA; however, tissue O2 extraction increased such that VO2max was not affected. Aten did not influence Qmax or any other parameter of systemic O2 transport in A. In conclusion the increased cholinergic tone may be responsible for the lower resting fH but not the lower fHmax of A; the integrity of the beta-adrenergic system is not necessary to attain VO2max in hypoxia either in A or in NA; the decreased response to beta-adrenergic stimulation in A limits the efficacy of this system on the mechanisms of systemic O2 transport and reduces the effect of its blockade on these mechanisms.