1. The role of carbonic anhydrase near the medullary chemoreceptors has been investigated in the cat. Vertebral artery injections have been used to cause abrupt changes in respiration as a result of changes in the activity of medullary chemoreceptors. 2. Injections of 100% CO2-saline were used to stimulate respiration and of Tris or alkalinized albumin solution to cause a reduction in respiration. 3. The injections gave rapid effects. We studied the effect on these of benzolamide (1-4 mg/kg i.v.) a carbonic anhydrase inhibitor which does not easily cross the blood-brain barrier and acetazolamide (50 mg/kg i.v.) an inhibitor which crosses the barrier more easily. 4. The effects of Tris were much reduced after benzolamide. Even addition of benzolamide to the injected Tris or albumin was sufficient to reduce their effects. 5. The effects of CO2-saline were reduced only after acetazolamide i.v. Whereas addition of carbonic anhydrase to injected Tris potentiated the effects on respiration, after acetazolamide this potentiation was much less marked. 6. It is concluded that carbonic anhydrase acts in the region of the medullary chemoreceptors at two sites: (a) outside the blood-brain barrier, probably at the luminal surface of the capillary endothelium, where it may act on plasma buffers, and (b) inside the barrier, in association with the chemoreceptors, where it may accelerate CO2/pH equilibration.