That caffein may give rise to different effects in various species of animals was observed for the first time by Bennett.(9) He studied its action on frogs, mice, rabbits, and cats, and attempted to determine the minimum fatal dose in rabbits and cats. He also reported experiments with thein. In his first communication on the subject he states that the administration of thein to rabbits first increased and then diminished the frequency of respiration, while the pulse was decreased in frequency. Caffein, which he apparently thought was different from thein, caused increased frequency of respiration, while the pulse was markedly retarded after a preliminary acceleration. He also noticed congestion of the ears, muscular incoordination, tetanus, paralysis, diminished reflexes, and contraction of the pupils. Bennett reported the minimum fatal dose of caffein for a rabbit weighing 3.25 pounds as being 5.25-5.5 grains. The symptoms in cats after the administration of toxic doses of thein or of caffein were great excitement, paralysis alternating with convulsions, and profuse salivation. The minimum fatal dose for a cat weighing 5 pounds was, according to Bennett, 6 grains of caffein and 5.5 grains of thein. Only one experiment on a mouse is reported; the administration of 0.1 grain proved fatal. The symptoms were the same as those observed in cats and rabbits after the administration of caffein. The experiments on frogs indicate that the symptoms were about the same as those previously described in the case of warm-blooded animals except that the reflexes are almost completely lost after the subcutaneous injection of doses of one-sixteenth to one-twelfth of a grain. The latter dose was fatal for frogs. It would be of interest to know the comparative toxicity of caffein to frogs and mammals, but unfortunately the weights were not reported. Schmiedeberg(79) (1874) noticed that the administration of 20 mg of caffein to frogs weighing about 45 grams was followed, in _Rana esculenta_, in about 25 minutes, by increased reflexes, 7 minutes later by tetanus. Several attacks occurred, but tonic spasms were never observed. On the contrary, when the same amount of caffein was given to _Rana temporaria_ weighing 45 grams he noticed a marked diminution of the reflexes and tonic rigidity of the muscles after 23 minutes; the reflexes were greatly increased, however, about 24 hours later. The frogs were under observation for three days, and although symptoms were still present at the end of this time in the subjects of both species tetanus was never observed in _Rana temporaria_.