The recent investigations of Patek and Stetson (1) 2 indicate that the defect in coagulation of blood in hemophilia resides in the plasma rather than in the platelets. Patek and Taylor (2, 3) 2 isolated a substance from citrated normal cellularfree plasma, by isoelectric precipitation, with which was associated the clot-promoting factor of normal plasma. This substance was effective, both in vitro and after intravenous injection, in reducing the coagulation time of hemophilic blood. By the same method, a similar substance in approximately the same quantity was obtained from citrated hemophilic plasma, but its clotaccelerating power on hemophilic blood was much less marked. In the absence of definite knowledge concerning the nature of the effective material it was called "globulin substance " which is the nomenclature that will be retained in this communication. The material was thermolabile, insoluble in water, partially soluble in physiological saline solution, and non-diffusible. It was precipitated in optimal amounts between pH 5.9 and 6.4. The material passed readily through a Berkefeld filter without loss of potency and was almost completely inactivated by small excesses of alkali (3). Bendien and Creveld (4) have isolated a substance, by dilution and acidification, from normal serum which they injected intramuscularly and intravenously and report favorable results.Patek and Taylor's (3) studies imply that in some respects hemophilia is a deficiency disease in which certain factors present in normal cellular-free plasma are either reduced or modified. The present communication reports a study of the effects of intramuscular administration of 1 The expenses of this research were defrayed in part by a gift to Harvard University from Smith, Kline and French Laboratories of Philadelphia.2 Review of literature here.globulin substance on the blood coagulation time of hemophilic subjects, and on the content of a clot-promoting factor in the blood following such administration. METHODSCoagulation time. In general the standard procedure followed was the same as that used in previous studies (1,3) When test substances were to be assayed they were pipetted into the test tubes prior to the addition of the blood. Further mixing was not found necessary.Immediately after the addition of whole blood, duplicate tubes were placed in a water bath at 37.50 C.

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