Sows were made tolerant to Escherichia coli endotoxin by daily intravenous (IV) injection of the pyrogen. A refractory state was induced, characterised by a markedly decreased fever. In contrast, intramammary (IMM) infusion of only a quarter of the endotoxin dose to which the animals were made tolerant by IV injection produced a markedly increased fever. This finding suggests that inflammatory endogenous mediators were released in the mammary glands and that their subsequent absorption into the blood circulation, and not the absorption of endotoxin caused fever.