Peretti's(70) (1875) studies on the effects of caffein were confined chiefly to observations on dogs. He also made observations on a few rabbits and reported an experiment on one cat to which he administered, by subcutaneous injection, 0.18 gram of caffein per kilo and noticed increased frequency in lachrymation and crying. The cat was found dead the next day. The subcutaneous injection of a rabbit in which artificial respiration was instituted with 0.36 gram of caffein per kilo proved fatal soon after the injection without any manifestation of symptoms. Small doses of caffein, 0.1 gram, given to a rabbit weighing 3,670 grams, failed to produce any visible effects. Doses under 0.1 gram per kilo likewise failed to induce any symptoms in dogs. When 0.1 gram of caffein per kilo was given by mouth or subcutaneously it was followed by restlessness, salivation, rigidity of hind legs, and vomiting. In both instances the dogs recovered. The symptoms were more severe when the dose was increased to 0.185 gram per kilo, but even in this case the dog recovered. A dose of 0.2 gram per kilo, however, proved fatal. Henneguy(36) (1875) experimented on three frogs to which he gave 0.01 gram of caffein citrate subcutaneously. He observed mild stimulation of the nervous system and of the muscles, as well as increased cardiac activity. Later, voluntary movement and respiration disappeared and sensations diminished, but convulsions of the extremities appeared. Cardiac activity was then diminished, the heart being finally arrested in systole. Since the motor nerves retained their irritability even after the reflexes disappeared, he concluded that the loss of motion was due to the action of caffein on the nerve centers. Binz(11) (1878) reported experiments on dogs and also made some observations on man with caffein. The subcutaneous injections of 0.2 gram caffein may prove fatal to dogs, although some survive such a dose. The toxic dose in man varies from 0.5 to 1.5 grams. Disturbance of the circulation, such as palpitation of the heart and fullness of pulse, restlessness, and diarrhea were the symptoms he observed.