An attempt is made to describe the nature of the chemical interactions participating in blood clotting. In the laboratory, thrombin can be derived directly from prothrombin without the physiologic activators calcium, thromboplastin, Ac-globulin, and platelet derivatives. The newly recognized clotting factor, Ac-globulin, is essential for normal physiologic hemostasis. Plasma Ac-globulin concentration decreases in experimental liver damage, temporarily with dicumarol administration and may increase from high doses of aminophylline. In citrated storage plasma it is stable for a week but not in oxalated human plasma. Compared with other species, human plasma contains a low concentration of Ac-globulin. Methods for Ac-globulin analysis have been developed; perhaps more important is the fact that the two-stage method for prothrombin analysis need no longer be considered a complicated procedure.