Twenty-one subjects were exposed to 1.5% CO2 in 21% O2 for 42 days with pre- and postexposure periods on air for 9 days. Respiratory minute volume (Ve) and alveolar pCO2 were increased throughout the exposure to CO2. After transition to air Ve decreased, while pCO2 remained elevated for 9 days. CO2 retention with uncompensated respiratory acidosis lasted for 23 days. CO2 excretion was increased during the 9-day recovery period indicating release of CO2 from the CO2 stores. Oxygen consumption did not change significantly during the experiment. Respiratory acclimatization to CO2 involved a continuous increase in tidal volume while the respiratory rate declined slowly after an initial increase. Changes in respiratory pattern were associated with an increase in physiological and anatomical dead space. A significant increase in the arterial-alveolar pCO2 and alveolar-arterial pO2 gradient indicated the development of an alveolar dead space. The ventilatory response to 5% CO2 was markedly reduced at the end of CO2 exposure. chronic CO2 exposure; chronic hypercapnia; chronic respiratory acidosis Submitted on August 31, 1961