This brings us to a consideration of the behavior of caffein in chronic intoxication. Although in both rabbits and dogs absence of cumulation was evident, in other respects decided differences in the resistance to caffein were observed. While the rabbit tolerates more than twice the single dose of caffein per kilo for the dog, the result is quite different in repeated dosage of the drug, the rabbit succumbing to continued administration of much smaller doses of the drug than the dog. This is probably due to lesions of the gastro-intestinal canal caused by caffein which occasions loss of appetite much more readily in the rabbit than in the dog. The abundant energy reserve in the dog makes it possible for this animal to stand inanition much longer than the rabbit and other herbivora. The difference in the behavior of the rabbit and dog toward caffein is interesting as showing complete reversal of resistance in acute and chronic intoxication. From the statement in the introduction it is evident that the size of the single toxic or lethal dose of a substance is in no wise an index of the active degree of its toxicity. The experiments with caffein here reported furnish additional evidence that this is true, at least for the rabbit. GENERAL SUMMARY AND CONCLUSIONS. The toxicity of caffein in the rabbit varies with the mode of its administration, being least when given by mouth and greatest by intravenous administration. The toxicity is from 15 to 20 per cent greater by subcutaneous injections than by mouth, but is about half of that when injected into the peritoneal cavity. No difference was observed in the toxicity of caffein whether administered into gluteal or into the lumbar muscles. When introduced by this route the toxicity was found to be less by one-third than when it is injected into the peritoneal cavity, but is about 30 per cent more toxic than the subcutaneous injections. White or black rabbits were found to be less resistant to caffein than gray rabbits. The resistance of the guinea pig to caffein, as of the rabbit, is greatest when given by mouth. The minimum fatal dose is less by intraperitoneal injections, but greater than by subcutaneous injections, thus differing from the rabbit in this regard. The adult cat is less resistant than the guinea pig or rabbit to caffein. The minimum lethal dose by mouth is the same as by subcutaneous, and is less than by intraperitoneal, injection. The minimum fatal dose for dogs was found to be the same by mouth as by subcutaneous injection and is almost the same as for the cat. The toxicity of caffein varies in the guinea pig according to season of the year.