When this topic, nonspecific resistance to infectious disease, first came under the author's consideration it seemed quite possible to group many factors affecting disease resistance into the nonspecific category. At first thought, penicillin, botulinus toxin, and climatic differences might be considered such agents. Penicillin affects several species of bacteria in several hosts. Botulinus toxin sickens several hosts. Climate seemingly changes many diseases. Further thought showed that the problem was much more complicated if the actual operation of any of these agents was traced to the mechanism through which it acted in causing resistance or susceptibility. It was true that the action of each of these agents spread over a number of species but in these species the vulnerable point was generally found in some common physicochemical reaction extending throughout the group. This common method of action would be expected if consideration is given to how the disease process could arise. In evolutionary times differentiation took place, making different members of the then living group capable of fitting into different climatic or other conditions. The initiation of these differentiations probably took origin in specific mutations, which control specific mechanisms in the developmental pattern not only of the individual with the inheritance but also in progeny to come. As a result, rivers of like physicochemical reactions flowed out to what ultimately became different species. Similarly pathogens developed and expanded through the incorporation of some change in their organization which gave them the ability to invade a specific host. Again the process was comparable to gene mutation. Ever-present selection refined the processes by which the organism became pathogenic on those species which had the specific characteristic to interact specifically with the newly acquired property.