The secretion of alkali metal ions by the perfused cat pancreas as influenced by the composition and osmolality of the external environment and by inhibitors of metabolism and Na+, K+-ATPase activity.

1. The secretion of sodium, potassium and lithium has been studied in the isolated cat pancreas, perfused with bicarbonate buffered saline solutions of varying composition and osmolality, and stimulated maximally with secretin.2. Under isosmolal conditions, when perfusate sodium chloride was replaced by sucrose, sodium secretion and potassium secretion were directly related to perfusate sodium concentration, [Na](p).3. When osmolality was varied by increasing or decreasing perfusate sodium chloride concentration, the secretion of sodium and of potassium were maximal at [Na](p) of about 120 and 80 mM respectively.4. At a given [Na](p), sodium secretion was greater under hypo-osmolal conditions than under isosmolal conditions.5. When potassium concentration was varied over the range 0-130 mM under isosmolal conditions, by adjusting perfusate NaCl concentration, the secretion of potassium and of sodium were maximal at [K](p) of about 50 and 10 mM respectively. Water flux was maximal at a [K](p) of 10-15 mM. The concentration of potassium in the secretion was almost identical with that in the perfusate over the whole concentration range.6. Replacement of perfusate sodium by lithium reduced the volume of secretion, though a small secretion was maintained even in the complete absence of sodium. The concentration of lithium in the secretion was generally slightly greater than that in the perfusate.7. Omission of potassium from the perfusate reduced secretion by about 65%. Rubidium was a complete substitute for potassium; caesium was not.8. Energy for secretion is derived largely from oxidative phosphorylation. Secretion was reduced by more than 90% under anaerobic conditions and in the presence of dinitrophenol or cyanide. Removal of glucose from the perfusate reduced secretion by more than 50% within 30 min; lactate was a complete substitute for glucose.9. Ouabain, ethacrinic acid and frusimide, known inhibitors of Na(+), K(+)-ATPase activity, all inhibited pancreatic electrolyte secretion.10. The observations are interpreted with reference to the nature of active transport processes involved in pancreatic electrolyte secretion.