According to Gentilhomme(27) (1867), after caffein the reflexes are at first diminished and then disappear altogether. Death is produced by stiffness and immobility of all the muscles, particularly of the muscles of respiration, thus causing asphyxia. He furthermore held that caffein has no effect on cardiac or smooth muscle fiber, its action being specific on voluntary muscle fiber, contractions of which he observed under the microscope, thus differing completely from strychnin, which is a nerve poison. These observations seemed to be confirmed by Pratt(74) (1868), who reported that the isolated posterior extremities and muscle fibers of the toad placed in a solution of caffein (1 grain to a wineglassful of water) for three minutes were contracted, while controls placed in distilled water were relaxed. This experiment is, of course, defective, as normal salt solution should have been used in both cases. When the muscular fibers previously immersed in caffein solution were placed under the microscope violent contractions were observed. The same author administered from 2 to 18 grains at a dose to five healthy young men. After the administration of 12 grains he noticed mental anguish, tremors of the hands and arms, and insomnia. Doses under 5 grains had no marked effect except a diminution in the frequency of the pulse and wakefulness. About the same time Amory(4) (1868) published the results of his studies on the toxicity of caffein in cats, dogs, rabbits, and pigeons. In all cases very large doses were introduced directly into the stomach by means of a temporary gastric fistula. Ten grains given in meat to a dog caused restlessness, but no other symptoms. Doses of 30 grains and above were invariably fatal. Seventy-three grains given to a cat caused death within 20 minutes. From observations on frogs, guinea pigs, rabbits, and on one dog, Leven(53) (1868) concluded that caffein which he gave in the form of the citrate in doses of 10 mg to frogs, from 150 to 200 mg to guinea pigs, and three to four times the latter amount to rabbits, stimulates the central nervous system and the voluntary, cardiac, and smooth muscles. He found that 0.9 gram caffein was fatal for a rabbit when injected subcutaneously, while 1 gram of the citrate was not toxic for a dog of medium size. Caffein applied directly to muscle fiber causes tetanus and destroys muscular contractility, while a nerve fiber similarly treated loses its irritability.