Intraperitoneal injections of Escherichia coli endotoxin in albino rats produces a decrease in food and water intake and a drop in body temperature. The drop in temperature and in water intake is probably proportional to the size of the dose. Using a behavioral test in which animals are trained to press a bar at a steady rate for intermittent food or water reward, it is possible to demonstrate the sudden onset of the toxin effect at 30 to 45 minutes after injection. In any group of rats, all of whom were presumably exposed to E. coli, three types of response to toxin can be found: (a) Sharp reduction in water intake 30 minutes after injection. (b) Little or no change in intake or rate of working for water reward. (c) Immediate depression of work rate. These three types of reaction appear related to previous experience with the toxin. The "normal" or "inexperienced" reaction a was seen in animals who had not been given toxin before. The "protected" reaction b, with little or no effect of toxin injection on response rate was frequently found 4 to 5 days after a previous injection. The "susceptible" reaction c was found in three animals after 14 or more days had passed since a previous injection. Injections of toxin into the lateral hypothalamic region of four animals through implanted cannulae had no effect on the rate of bar pressing for water. Control injections of lidocaine blocked response rate completely for brief periods in three animals.