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1. The rate of secretion from a saline-perfused preparation of the cat's pancreas is directly proportional to the perfusate bicarbonate concentration. When all bicarbonate is omitted, secretion completely or almost completely ceases.

2. Incorporation of [¹⁴C]bicarbonate into the perfusion fluid results in its prompt appearance in the juice. The radioactive label is concentrated four to five times in the juice just as the total juice bicarbonate is four to five times greater than perfusate bicarbonate.

3. These two observations suggest that about 95% of pancreatic juice bicarbonate is derived from perfusate (plasma) bicarbonate.

4. The inhibition of pancreatic secretion from the perfused gland by acetazolamide is similar to that observed in the intact animal.

5. There is a fall in pH and rise in P_CO2 in the perfusion fluid leaving the gland which is greater during secretion than at rest.

6. It is therefore suggested that during secretion, hydrogen ions pass from the gland into the perfusate (plasma), thus increasing the production of carbon dioxide from circulating bicarbonate. This carbon dioxide diffuses into the cell, is rehydrated (partly under the influence of carbonic anhydrase) and finally is secreted, thus establishing the necessary gradient for the continued diffusion of carbon dioxide into the cell.