Blood lactate and pyruvate levels and lactate-pyruvate ratios were determined in 20 patients with severe hypoxemia due to pulmonary insufficiency, 18 patients having arterial oxygen tensions (pO2) lower than 50 mm. of mercury, and 8 having tensions lower than 40 mm. of mercury. Most of the patients had normal lactate levels and lactate-pyruvate ratios in spite of severe hypoxemia, and there was no correlation between pO2 or oxygen content and raised levels. All but 1 patient with an elevated lactate level and lactate-pyruvate ratio had a disorder of systemic circulation with hypotension. On the other hand, failure of the right side of the heart with cor pulmonale did not lead to hyperlactatemia. In the resting state generalized tissue hypoxia and increased anaerobic metabolism are seldom due to clinical hypoxemia per se. When present, increased anaerobic metabolism is related to a systemic circulatory disorder, with resultant inadequate tissue perfusion.