Investigations in chronic obstructive pulmonary disease (COPD) patients have shown impaired glucose tolerance in hypoxic COPD patients, compared with COPD patients with normal arterial blood gases. In healthy subjects, hypoxaemia or stay at altitude, have been shown to alter glucose metabolism. At altitude the effect seems to be dependent on duration of stay. A short stay is associated with insulin resistance, a longer stay gives rise to increased glucose uptake. The euglycaemic hyperinsulinaemic glucose clamp technique is a method to study glucose tolerance and enables determinations of glucose clearance in peripheral tissues. We investigated six COPD patients [forced expiratory volume in 1 s 0.7 +/- 0.2 l (mean +/- SD)] with chronic hypoxaemia (PaO(2) 7.9 +/- 0.6 kPa at rest, breathing air), with and without oxygen supplementation, using the glucose clamp technique. Net peripheral glucose uptake was 5.5 +/- 1.2 and 7.1 +/- 1.6 mg (kg*min)(-1) (+29%) breathing air and supplemental oxygen, respectively (P = 0.03). The tissue sensitivity to insulin increased 32% (P = 0.03) with oxygen supplementation. The results indicate that normalization of oxygen saturation in COPD patients with chronic hypoxaemia may have an immediate effect on glucose tolerance and tissue sensitivity to insulin in these patients.