We have studied the CO 2 permeability of the erythrocyte membrane of the rat using a mass spectrometric method that employs 18 O-labelled CO 2 . The method yields, in addition, the intraerythrocytic carbonic anhydrase activity and the membrane HCO 3 - permeability. For normal rat erythrocytes, we find at 37 °C a CO 2 permeability of 0.078 ± 0.015 cm/s, an intracellular carbonic anhydrase activity of 64,100, and a bicarbonate permeability of 2.1 × 10 -3 cm/s. We studied whether the rat erythrocyte membrane possesses protein CO 2 channels similar to the human red cell membrane by applying the potential CO 2 channel inhibitors pCMBS, Dibac, phloretin, and DIDS. Phloretin and DIDS were able to reduce the CO 2 permeability by up to 50%. Since these effects cannot be attributed to the lipid part of the membrane, we conclude that the rat erythrocyte membrane is equipped with protein CO 2 channels that are responsible for at least 50% of its CO 2 permeability.