We studied the histomorphological changes of organs in an animal model of endotoxin tolerance (ETT). ETT was induced by pretreating pigs with increasing doses of endotoxin (ET) before challenging them with a continuous lethal ET infusion. In the ETT group the survival time was prolonged significantly versus controls, so that in the ETT group on an average double the ET challenge dose was administered. In this histomorphological study the lung, kidney, and intestine of almost all animals (ETT group n = 12, controls n = 11) showed about the same unspecific histological shock features. In the liver, however, we diagnosed partly disseminating, partly confluent, but obviously ET-induced, neutrophil liver cell necrosis in 10/12 ETT pigs and in 10/11 controls. We conclude that ETT in our model was not a protective factor against serious liver cell injury after ET administration. Our results may indicate that the ETT phenomenon can be overcome by raising the ET challenge dosage.