Changes in acid-base balance modify the secretory capacity of the rectal gland. Acidosis has an inhibitory effect, while alkalosis has an opposite, stimulatory effect. It has been known for some time that the rectal gland has a very large amount of carbonic anhydrase, but its inhibition with several different pharmacological agents did not show any effect on the secretion of chloride under diverse conditions both in vivo and in vitro, even where carbonic anhydrase was confirmed to be inhibited. The role of carbonic anhydrase in the secretion of chloride by the rectal gland was uncovered when experiments in live animals showed that, in glands that were stimulated to secrete, the inhibition of carbonic anhydrase reduced the secretion of chloride. That observation led to the understanding that under in vivo conditions, carbonic anhydrase is necessary for the removal of intracellular CO2 that is produced by the metabolic activity required to secrete chloride when the gland is activated. When the removal of CO2 is not restricted as in the in vitro conditions, the effect of inhibiting carbonic anhydrase is not seen.