According to Johansen(44) (1869), caffein acts directly on the muscular fiber. After the subcutaneous injection of 0.02 gram of caffein into frogs, he observed contraction of the muscles at the site of injection, then contraction of the anterior extremities, and finally the posterior extremities become rigid and extended. Johansen observed muscular rigidity after caffein, even after curara was injected, or after ligating the vessels, or cutting the nerves which supply the muscles. He also observed that large doses of caffein diminish muscular irritability. When cardiac muscle was poisoned with caffein, microscopical examination showed that the striations disappeared. Johansen also states that reflexes disappear after caffein poisoning. He never observed tetanus in frogs, but reported tonic and clonic convulsions as a result of caffein poisoning in mammals. Somewhat different effects of caffein in frogs were observed by Buchheim and Eisenmenger(14) (1870). After the injection of 2 per cent of the citrate the frogs soon become inactive. He also observed muscular twitching of the extremities, which gradually increased, with rigidity of the muscles and opisthotonos, while respiration became slow and superficial, finally stopping altogether. Aubert(6) (1872) studied the toxicity of caffein in man and other animals. After the ingestion of 0.36 gram, he observed dizziness, but doses of 0.12 and 0.24 gram were without any apparent effect. On the other hand, a dose of 0.5 gram of caffein was followed by increased frequency of the pulse, which soon disappeared. After one hour he noticed dizziness and trembling of the hands, which likewise passed away soon. The injection of 0.16 gram of a 2 per cent solution of caffein into the jugular vein of a rabbit weighing 1,090 grams caused tetanus and death in two and one-half minutes, and 0.12 gram injected into a rabbit weighing 980 grams caused death in one minute. Much larger doses could be borne, however, when artificial respiration was resorted to. A dog which was given 3 grams of caffein survived when artificial respiration was performed. Aubert reports, on the other hand, a similar experiment with 0.25 gram of caffein which terminated fatally.