Metchnikoff began by asking himself whether the microbes themselves did not produce antitoxins in order to defend themselves against enemy micro-organisms. He made many experiments but only obtained negative results, and concluded that the antitoxins must be manufactured by the organism itself. The origin of this property must be more recent than that of the phagocytic reaction, for it does not exist in plants or in inferior animals. It was only from superior cold-blooded vertebrates, such as the crocodile--and that only in artificial conditions--and upwards, that Metchnikoff succeeded in finding a specific antitoxic power in the humors. He ascertained that the vaccination of animals by toxins conferred, after a time, antitoxic powers to the blood and humors _which contained leucocytes_. He concluded therefrom that the presence of antitoxins depended on that of the phagocytes. Experiments on divers higher animals having proved that, in them also, antitoxins were localised in _humors containing phagocytes_, Metchnikoff concluded that the antitoxins were manufactured by the cells themselves. As toxins are absorbed and digested chiefly by _macrophages_, it is probable that it is the latter also which manufacture specific antitoxins, or the final product of the digestion of corresponding toxins. Metchnikoff could only propound this idea as an hypothesis, for the complexity and difficulty of a material demonstration did not yet allow of a definite solution of the problem. However, certain observations on toxins and antitoxins pleaded in favour of this thesis. For instance, working in collaboration with MM. Roux and Salimbeni, he had found that it is by soluble poisons that the cholera vibrions harm the organism or kill it, but that small doses of the same _poisons_ are vaccines and make the blood of the vaccinated animal _antitoxic_. On the other hand, a _microbian_ vaccination is preventive against _microbes_ only but not against toxins and the blood does not become antitoxic. This is explained by the fact that it is not the same cells which digest cholera microbes and cholera toxins: the _microphages_ digest the vibriones whilst the _macrophages_ digest the poisons and, probably, manufacture as products of this digestion, the corresponding antibody, the cholera antitoxins. On the contrary, in cases of the inclusion of _microbes_ by _macrophages_, as, for instance, in plague, the blood acquires an _antitoxic_ power by injection of the microbes themselves and not by their toxins, as was demonstrated by M. Roux and his collaborators. The same fact was observed by Metchnikoff on the alligator, in whom also microbes are digested by _macrophages_. In those cases, when microbes and toxins are digested by the same cells, the latter manufacture antibodies against both. These facts rendered legitimate the supposition of the macrophagic origin of antitoxins. * * * * *