Serum has no inhibitory effect on the formation or action of plasma thromboplastin, but is capable of its destruction or inactivation. Conditions influencing this hitherto unknown property have been studied. The action of the responsible agent is retarded at temperatures below 37[degree]C, is rapidly lost following dilution and is counteratced by excess factor V. In contrast, the clotting activity of tissue extract was not influenced by serum, suggesting that a different clotting mechanism is involved. The importance of these observations in the understanding of the forces implicated in the formation of plasma thromboplastin is discussed.