Experiments in incubation of various blood sera and kidney extracts produce the following effects on coagulation of dog heparinized plasma: (a) marked inhibition of clotting preceded in some cases by acceleration; (b) marked acceleration of clotting. Evidence points to the development of 2 substances in mixtures of serum and extract, one causing inhibition and the other acceleration of coagulation; both form through combinations of precursor substances in blood sera and tissue extracts. Accelerating and inhibiting precursor substances are both present in all sera and extracts tested, but they vary in amount or activity in different species. The effect of the mixtures on coagulation is the resultant action of these 2 substances. There is evidence of a specific adaptation between both accelerating and inhibiting substances. The inhibiting precursor substances tend to disappear in the blood serum of P-poisoned dogs.