In order to determine the mechanism whereby secretin is removed from the circulation, a series of expts. was conducted to investigate the possibility of secretin destruction by the blood. Mixtures were made of a standard amt. of secretin soln. with dog''s whole blood, serum, plasma, and washed cells, and these were incubated at 37[degree]C. for varying periods of time, then secretin potency was assayed on anesthetized dogs with the pancreatic duct cannulated. The incubation resulted in a progressive destruction of secretin by whole blood, plasma, and serum, and not by washed cells. The secretin-inactivating agent was destroyed by heating to 60 [degree]C. for half an hr.; its optimal temp. was 35-40[degree]C; its optimal pH was 7-7.5, and it was effective only in the pH range of 5 to 8. Outside this range it was inactivated, but not destroyed. The extent of secretin inactivation depended on the amt. of serum used. Secretin is probably destroyed by the blood and the mechanism is an enzymic one, indicating the presence in blood of an enzyme termed secretinase. The mode of action of secretinase is at present unknown; but it is certain that it is not a proteolysis.