Acclimatization to hypoxia has minimal effect on maximal O-2 uptake ((V)over dotO(2 max)). Prolonged hypoxia shows reductions in cardiac output ((Q)over dot), maximal heart rate (HR-(max)), myocardial beta-adrenoceptor (beta-AR) density, and chronotropic response to isoproterenol. This study tested the hypothesis that exercise training (ET), which attenuates beta-AR downregulation, would increase HRmax and (Q)over dot of acclimatization and result in higher (V)over dotO(2 max). After 3 wk of ET, rats lived at an inspired PO2 of 70 Torr for 10 days (acclimatized trained rats) or remained in normoxia, while both groups continued to train in normoxia. Controls were sedentary acclimatized and nonacclimatized rats. All rats exercised maximally in normoxia and hypoxia (inspired PO2 of 70 Torr). Myocardial beta-AR density and the chronotropic response to isoproterenol were reduced, and myocardial cholinergic receptor density was increased after acclimatization; all of these receptor changes were reversed by ET. Normoxic (V)over dotO(2 max) (in ml.min(-1).kg(-1)) was 95.8 +/- 1.0 in acclimatized trained (n = 6), 87.7 +/- 1.7 in nonacclimatized trained (P < 0.05, n = 6), 74.2 ± 1.4 in acclimatized sedentary (n = 6, P < 0.05), and 72.5 +/- 1.2 in nonacclimatized sedentary (n = 8; P > 0.05 acclimatized sedentary vs. nonacclimatized sedentary). A similar distribution of (V)over dotO(2 max) values occurred in hypoxic exercise. (Q)over dot was highest in trained acclimatized and nonacclimatized, intermediate in nonacclimatized sedentary, and lowest in acclimatized sedentary groups. ET preserved (Q)over dot in acclimatized rats thanks to maintenance of HRmax as well as of maximal stroke volume. (Q)over dot preservation, coupled with a higher arterial O2 content, resulted in the acclimatized trained rats having the highest convective O2 transport and (V)over dotO(2 max). These results show that ET attenuates beta-AR downregulation and preserves (Q)over dot and (V)over dotO(2 max) after acclimatization, and support the idea that beta-AR downregulation partially contributes to the limitation of (V)over dotO(2 max) after acclimatization in rats.