The object of these experiments was to determine the resistance to caffein in various species of animals and by various methods of administration. Caffein was therefore given by mouth and injected subcutaneously into the peritoneal cavity, into the muscles, and intravenously. As far as could be judged by appearance, healthy animals were selected for the subjects of the experiments, but as it is impossible to diagnose with any degree of accuracy the condition of the animal while it is alive, post mortem examinations were resorted to in many cases in which the issue of the experiment was fatal. Since the age of the animal may modify toxicity full grown, as well as young, animals were employed for these experiments; diet, race, and season also play an important part in determining the toxicity of a drug and these factors were also taken into account in the present investigation. EXPERIMENTS ON RABBITS. Animals of different varieties were used and were given caffein by all of the methods indicated in the preceding paragraph. Some of the rabbits employed in these experiments received oats, others received a diet exclusively of carrots for several days or weeks previous to the administration of caffein. The experiments were conducted at all seasons of the year. SUBCUTANEOUS INJECTION. From a study of the literature on the toxicity of caffein it seemed that about 150 mg per kilo is probably the lethal dose for the rabbit when the drug is injected subcutaneously. Preliminary observations were therefore carried out with such a dose, but it was found, on the contrary, that this amount per kilo was hardly sufficient to induce symptoms in the great majority of cases. SERIES A. [Doses of 147 to 167 mg of caffein per kilo were employed in these experiments.] _Rabbit 332. Belgian hare, female. Weight, 1,070 grams. Diet, oats._ March 25: 8.5 cc 2 per cent caffein (158 mg per kilo) injected subcutaneously at 2.15 p. m.; 4 p. m., reflexes increased; 5.45 p. m., increases of reflexes still more marked. March 26: Rabbit looked normal; no symptoms observed. _Rabbit 331. Belgian hare, female. Weight, 1,170 grams. Diet, oats._ March 25: 2.15 p. m., 9 cc 2 per cent caffein (153 mg per kilo) injected subcutaneously; 4 p. m., reflexes increased; 5.45 p. m., condition the same. March 26: Rabbit looks normal; no symptoms observed. _Rabbit 328. Belgian hare, female. Weight, 1,200 grams. Diet, oats._ March 25: 9 cc 2 per cent caffein injected subcutaneously (150 mg per kilo); 4 p. m., reflexes increased; 5.45 p. m., reflexes increased but not markedly. March 26: No symptoms; rabbit looks normal. _Rabbit 322. White female. Weight, 1,065 grams. Diet, oats._ March 17: 8 cc 2 per cent caffein (150 mg per kilo) injected subcutaneously at 11.55 a. m.; 12.55 p. m., reflexes increased, but no tetanus nor any other symptoms. March 18: Rabbit running around in cage; condition apparently normal. March 25: Condition of rabbit good.