In 30 patients with respiratory insufficiency due to chronic obstructive pulmonary disease and with normal red blood cell counts, the effect of hypoxia on erythropoiesis was studied. Pronounced hypoxaemia was ascertained in all the patients by measuring PaO2. The calculated HbO2 saturation was less than 85% in group I and greater than 85% in group II, each consisting of 15 patients. Although the RBC counts and Hb concentration were within the limits of normal values, the packed RBC volume was higher than 45% in all the patients tested. The calculated MCV was increased and the erythropoietin level in plasma, indirectly measured in polycythaemic mouse bioassay, was higher than normal. Macrocytosis was shown to be PaO2-dependent and should be, according to Stohlman's data, the result of erythropoietin excess and the subsequent cessation of nucleic acid synthesis with skipped terminal division of erythroblasts in the bone marrow. The absence of erythrocytosis in these patients could be explained by a shortened survival time of macrocytes and/or other causes.