The aim of the study was to investigate the effects of chronic hypoxaemia on neuroendocrine function in hypoxaemic chronic obstructive pulmonary disease (COPD). The stress level was assessed by measurement of daytime plasma catecholamine and nocturnal urinary catecholamine levels and endocrine function was assessed by measuring serum gonadotropins, peripheral sex hormones and peripheral thyroid hormones, and by measuring thyroid stimulating hormone (TSH), prolactin and growth hormone before and after thyroid releasing hormone challenge in 12 male, stable, hypoxaemic COPD patients before and after at least 4 months of long-term oxygen treatment (LTOT). Mean pre-treatment PaO2 was 7.39 +/- 0.78 kPa and mean nocturnal arterial oxygen saturation (MSaO2) was 86.6 +/- 3.2%. Plasma norepinephrine (NE) levels were higher than normal, while all other pre-treatment hormone levels were within normal range. Low forced expiratory volume in 1 sec (FEV1) was associated with low basal and stimulated TSH (P < 0.01). Urinary NE excretion correlated positively to nocturnal time spent with SaO2<85% (P<0.05). In similarity with normal controls, positive correlations were found between sex hormone binding globulin and testosterone both before and after LTOT (P<0.01). No significant hormonal changes were noted following an average of 8 months of LTOT for the entire study group. However, in a subgroup (n = 6) with an increase in MSaO2 exceeding 7% points following LTOT, nocturnal excretion of NE and epinephrine were reduced by 30% (P<0.05) and S-free thyroxin by 20% (P<0.05). In conclusion, patients with chronic hypoxaemia secondary to COPD exhibit elevated plasma NE levels but otherwise normal endocrine levels, including a normal hypothalamic-pituitary testicular axis. The severity of airway obstruction is associated with reduced basal and stimulated TSH. The endocrine function is not significantly changed following LTOT except for a subgroup with severe nocturnal hypoxaemia, where elevated nocturnal NE excretion was noted, which was reduced only if whole night oxygenation was normalized during oxygen therapy.