This study investigated glucose metabolism and glucose-mediated hormone responses in patients with chronic respiratory hypoxaemia. Glucose as well as insulin, glucagon, adrenaline, cortisol and growth hormone (GH) were measured before and at 30, 60 and 120 min during an oral glucose-tolerance test. The following chronic obstructive pulmonary disease (COPD) patients were studied: 10 normoxaemic (mean paO2 10.9 +/- 0.4 kPa), 10 hypoxaemic (mean paO2 7.6 +/- 0.2 kPa before, and 10.6 +/- 0.4 after 24-h oxygentherapy, and 6 hypoxaemic patients on long-term oxygen therapy (LTOT) (mean paO2 10.9 +/- 0.7 kPa before, and 7.1 +/- 0.3 after 4 h with less than 0.5 litre oxygen per minute). The hypoxaemic patients were tested both with and without (or reduced) oxygen therapy. Twenty healthy sex- and age-matched subjects served as controls. Plasma glucose at 120 min was significantly higher in LTOT patients than in controls (p < 0.01), normoxaemic patients (p < 0.01) or hypoxaemic patients (p < 0.01). The areas under the curve for plasma glucose and insulin were significantly higher in both the LTOT and hypoxaemic groups compared to controls (p < 0.01 and 0.05, respectively). Glucose values for normoxaemic COPD patients were similar to those for controls. Glucagon, adrenaline, cortisol and GH levels did not differ significantly between the groups. A 4-h low-dose or oxygen-free interval in the LTOT group or 24 h of oxygen supplementation in the hypoxaemic group did not affect glucose and hormone levels significantly. It is concluded that severely hypoxaemic COPD patients have altered glucose metabolism which cannot be readily explained by changes in gluco-regulatory hormones or short-term alterations in oxygenation.