Heart rate (HR) response to isoproterenol (ISO) infusion (IP) is decreased in normal sea level (SL) natives exposed to high altitude (HA). Since norepinephrine plasma concentration is higher in HA hypoxia, a downregulation of beta-adrenoceptors (beta AR) was evoked. We explored this phenomenon at 3600 m in a HA normal population (HAN) and in polycythemic subjects (HAP). Results are compared to SL natives in normoxia (SLN), and during chronic hypoxia at 4800 m (SLH) (J Appl Physiol 65:1957-1961, 1988). ISO dose required to raise HR by 25 min-1 (I 25) is not different in HAN or HAP group when compared to SLN. Density of beta AR on lymphocytes was 39% and 25% lower in HAN and HAP than in SLN group, respectively. Chronotropic response to IP is similar in SL and HA subjects under their usual environmental conditions, while SL natives show a blunted response under hypoxia, probably due to a decrease in beta AR density. No adrenergic desensitization was found in highlanders. Lower beta AR density in HA groups could be an adaptive mechanism to chronic hypoxia. Polycythemia does not affect this responsiveness.