In his general review of anaphylaxis, Besredka stated that an injection of horse serum into guinea pigs produced hypersensitization, only if minute doses were employed. “The preliminary injection of more than .02 cubic centimeter is attended by an uncertain result.” Similar statements abound in the literature. The great majority of the experiments on which these conclusions are founded have employed either the intracerebral or the intraperitoneal route for the intoxicating injections. If, however, the second injection is made intravenously, the results are entirely different. With this method, it can be shown that a preliminary injection of as much as five cubic centimeters of horse, or other serum, is invariably followed by a typical anaphylactic state, in which death is produced by the second injection of an amount of the same serum, which, for normal animals, is absolutely innocuous. If guinea pigs are given repeated large injections, e. g., 3 c.c. of horse serum, on three or four successive days, the total amounting to nine or twelve cubic centimeters, exactly the same result follows. Finally, if spaced injections are employed, as in the procedure followed for purposes of immunization, again the animals become typically anaphylactic. There are, however, certain differences in the behavior of animals sensitized, on the one hand, by means of minute, and, on the other, by very massive injections of serum. In the former, the minimal lethal dose is often no greater than .005 cubic centimeter of horse serum. In the latter, it is often one hundred times this amount. Again, after a small injection, anaphylaxis frequently does not develop for three weeks; after massive injections, it may generally be demonstrated in ten or twelve days.