_Autopsy (dog 31)_: Lungs congested; heart filled with blood and contained small amount of blood-stained fluid in pericardial sac. Liver deeply congested, soft and friable; gall bladder distended with bile; kidneys showed inflammation of cortex; spleen pale, normal in size and consistency; stomach practically empty, the mucosa of the pyloric portion exhibited severe gastritis, with thick catarrhal exudate. This catarrhal inflammation extended through the duodenum; remaining portion of small intestine showed mild inflammation; large intestine appeared practically normal. The total amount of caffein received by dog 31 during 10 days was 5.395 mg, or a daily average of 53.9 mg per kilo. This unusually low resistance to caffein (which was practically the only case in all the experiments on dogs presented in this research) suggests the presence of some abnormal condition. The bloody exudate in the pericardial cavity indicating pericarditis, which is likely to induce secondary changes of cardiac muscle, may be considered as a possible cause of the increased toxicity of caffein in this case. _Dog 29. Male fox terrier, black._ This dog was kept on a low nitrogen diet for nearly five weeks before the feeding of caffein was begun. The administration of 50 mg of caffein per kilo was then carried on for eight days without showing any symptoms of toxicity. The usual increase of dose was then given--75 mg per kilo--which was followed by a manifestation of symptoms. Further increase, however, to 100 mg per kilo had no visible effect. Nevertheless it was considered advisable to suspend the feeding of caffein for one day. The same amounts were then repeated on two consecutive days. No symptoms having been observed, 125 mg per kilo were given. As symptoms of toxicity and especially loss of appetite were observed, the dog was not given any caffein the next day. Since his appetite had now improved, the experiment with larger doses was resumed. Death followed after the second dose of 150 mg per kilo. Protocol follows: Weight, 9.90 kilos. One-third nitrogen diet. Receives 0.269 gram nitrogen per kilo (88.269 calories per kilo). November 3: Weight, 9.85 kilos. November 10: Weight, 9.55 kilos. November 12: Weight, 9.40 kilos. November 29: Weight, 9.85 kilos. December 6: Weight, 9.90 kilos; 11.35 a. m., received 25 cc 2 per cent caffein solution by subcutaneous injection in back; 4 p. m., no symptoms, appetite good. December 7-9: Received 25 cc caffein 2 per cent solution--subcutaneous injection, no symptoms, area of injection inflamed and swollen. December 10, 13: Site of injection showed increased inflammation, received 0.495 gram caffein (50 mg per kilo) in 30 grams meat daily without showing any symptoms. December 14: 12 noon, received 0.7425 gram caffein by mouth (0.075 per kilo); 2.30 p. m., restless and uneasy. December 15: 11.30 a. m., received 0.7425 gram caffein by mouth; 2 p. m., depressed in spirits, although continues to have good appetite.