Arterial oxygenation at rest and during maximal treadmill exercise was studied in a group of 17 patients with chronic obstructive pulmonary disease. Patients who developed exertional hypoxemia (subgroup 1) were compared to others who did not (subgroup 2). There was no significant difference between the 2 subgroups at rest in terms of mixed venous PO2, cardiac output, or venous admixture. Subgroup 1 had more severe respiratory impairment than subgroup 2, but there was marked overlap of their respective lung volumes and flows. Both subgroups showed the same extent of desaturation of mixed venous blood during maximal treadmill exercise, so that exertional hypoxemia cannot be explained on the basis of low mixed venous O2. The marked difference between subgroup 1 and subgroup 2 was that the latter showed decreased venous admixture on exercise. Because of the relative constancy of mixed venous blood desaturation, arterial saturation was closely correlated with venous admixture both at rest (r = 0.931) and during exercise (r = 0.985).