Effects of endotoxin on the motility, the permeability of mesenteric blood vessel and endogenous substances (electrolyte (Na, K), histamine, serotonin and primary prostaglandin) in the small intestine of mice were investigated. Diarrhea was induced by intraperitoneal injection of Salmonella typhosa endotoxin in mice. It is suggested that the diarrheal action of endotoxin is due to the acceleration of intestinal motility and/or the facilitation of mesenteric blood vessel permeability. On the other hand, from the observation of blood concentration of acetaminophen and sulfisoxazole, inhibition of drug absorption was suggested in cases of diarrhea induced by endotoxin. This inhibition of gastrointestinal absorption is due to the delay of the gastric emptying rate, the increase of intestinal transit time of drug in the absorption site and the acceleration of mesenteric blood vessel permeability. Then it is conceivable that these actions may be mediated by biogenic amines (serotonin and histamine) and primary prostaglandins.