In order to determine whether endotoxin is normally found in the portal system, intraoperative samples of portal and peripheral blood were drawn from 34 consecutive elective abdominal surgery patients. The limulus lysate test was used to detect endotoxin. Ninety-seven per cent of patients had a positive limulus test in portal blood. Twelve of these patients were tested for portal bacteremia and only one showed growth. Four patients also had systemic endotoxemia. Three of these had liver disease and one had a gram-negative sepsis. This study demonstrates that endotoxin is a normal constituent of portal venous blood in man and does not represent a pathological process. It is suggested that the Kupffer cells of the liver normally protect the systemic circulation from endotoxin, and that endotoxin is present in systemic blood only when liver function is impaired or gram-negative bacteremia is present.