It is known that cardiovascular diseases are the leading cause of morbidity and mortality in the western world. Recently it was observed that adaptation of myocardium to chronic hypoxia can contribute to the improvement of ischemic tolerance of myocardium. Chronic hypoxia can induce a wide range of adaptive changes in myocardium, which could be considered as cardioprotective, but exact molecular mechanism of these adaptive changes is still unclear. Adaptation to chronic hypoxia leads to increased activity of the sympathetic nervous system, thus increasing catecholamine levels in the body. The increased level of catecholamines and their effect on β-adrenergic signaling could contribute to the development of cardioprotection. Beta-adrenergic receptors (β-ARs) form an interface between the sympathetic nervous system and cardiovascular system and therefore they act as effective regulators of cardiac activity, which can be modulated by sympathetic transmitters. The aim of this study was to pursue changes in the β-adrenergic signaling in rat myocardium after adaptation to two different regimens of hypoxic conditions: 1/ intermittent normobaric hypoxia – INH/R (23 h hypoxia, 1 h reoxygenation) and 2/ continuous normobaric hypoxia – CNH (24 h hypoxia). We assessed the effect of adaptation to hypoxia on the total amount of β-ARs, the ratio of β-ARs subtypes (β1-ARs to β2-ARs) and activity of adenylyl cyclase (AC) in the left (LV) and right ventricles (RV). The results determined in the hearts from rats (male, 250-350 g, n=10 in each group) adapted to hypoxia were compared with those obtained in the corresponding normoxic animals. It was found that adaptation to INH/R and CNH was accompanied by a significant decrease (about 25%) in the total number of β-ARs in the RV. Although the statistical analysis (one-way ANOVA) revealed significant changes (decrease) in the ratio of β1-ARs to β2-ARs only for CNH model in the RV, there was a clear downward trend in the transcription and expression of β1-ARs in the RV from rats adapted to CNH or INH/R. Activity of AC was also affected by the adaptation of rats to INH/R and CNH. Whereas AC activity stimulated by different activators (GTPγS, NaF or forskolin) was increased in the LV, it was decreased in the RV. These results indicate that AC signaling may play an important role in the adaptive process to chronic hypoxia.