Pancreatic flow and HCO3– and Cl– output were studied in dogs following 2 U/kg (i.v.) of secretin. Acetazolamide reduced flow and HCO3– output to half normal. HCl produced the same effect. NaHCO3 increased flow and HCO3– output. CO2 produced little change. Severe hyperventilation decreased flow and HCO3– output. Results are consistent with secretion dependent on the over-all reaction OH– + CO2 → HCO3–, with both a carbonic-anhydrase catalyzed and an uncatalyzed component. Reduction of either reactant or of enzyme decreased output: increase of the reactants increased output. From in vitro kinetics and analysis of rates in vivo, the role of carbonic anhydrase may be assessed. About half of HCO3– output normally depends on the uncatalyzed reaction, and half on the catalyzed. In metabolic alterations, only the uncatalyzed component is affected. Pancreatic carbonic anhydrase is greatly in excess of that needed for the observed catalyzed rate in vivo. Correspondingly, reduction of output by acetazolamide occurs only when >99% of pancreatic carbonic anhydrase is inhibited. It is suggested that the rate-limiting event in pancreatic HCO3– secretion is transport of HCO3– from cell to duct.