Moderately large amounts of caffein fed daily to puppies for several days--in some cases as long as 10 days--induced mild symptoms only. No cumulative effect was observed in any of the experiments of series C. There seems to be tolerance of certain functions toward caffein, but no general tolerance of the body could be obtained in these experiments. Caffein is apparently less toxic for adult dogs on high than on low protein diet. In young and growing dogs caffein is somewhat less toxic when milk, rather than meat, forms the exclusive diet. Some pathological conditions apparently increase the toxicity of caffein also in dogs. The symptoms of caffein intoxication observed in young dogs are in some respects different from those in full grown and older animals, and resemble those noticed in rabbits. DISCUSSION OF RESULTS. It was pointed out at some length in the introduction that the toxicity of some drugs may not be the same for all forms of life. This observation was also made by some investigators who experimented with caffein on different species of animals. Thus Maurel(55) stated that caffein is twice as toxic for the frog as for the rabbit when administered by mouth. Fröhner's(26) experiments, on the other hand, made on domestic animals, failed to show great differences in the toxicity of caffein. According to this observer, horses seem to be more susceptible than cattle, goats, and swine, the minimum toxic dose being the same for all of these, while the resistance of the dog to caffein is about midway between that of the horse and the other animals mentioned. It may be remarked, however, that Fröhner made only 13 experiments. That these data are inadequate for the formation of any conclusions as to the toxicity of caffein is evident since the most striking effect of caffein observed in the work herein reported was the comparatively wide range of variation in the resistance of individuals of the same species to this drug. This was found to be the case even when the conditions of experimentation were approximately uniform, and was observed whatever the mode of administration of the drug employed. The toxicity for different individuals also varied in acute as well as in chronic intoxication. It is for this reason that the number of tests employed were often quite large, for no conclusions of any value could be drawn without averaging the results of a sufficiently large number of experiments. Furthermore, it is to be borne in mind that the action of a drug may differ according to the mode of its introduction into the body and that different species of animals may vary in this regard. This is especially true of some substances when given by mouth, the range in toxicity for certain species of animals being much greater when thus administered than when injected subcutaneously or intravenously.