Broth culture filtrate containing endotoxin, prepared from serotype O 139:K82(?):H1 was given by the intra-enteric route with and without dimethyl sulphoxide, and with or without blockade of the RES by intravenous injection of trypan blue, using about five piglets for each of the four combinations. Clinical signs, blood pressure, ECG, respiration, temperature, haematology and pathological findings were recorded. Coli enterotoxaemia manifested by fatal endotoxin shock developed in all ten piglets given toxin plus dimethyl sulphoxide, and in 4 of 5 similarly treated after RES blockade. The sondrmoe did not develop in piglets given large amounts of toxin without dimethyl sulphoxide, whether the RES was blocked or not. When enteric absorption of toxin was promoted by dimethyl sulphoxide, RES blockade increased the sensitivity of the animal to toxin (shortening of the time till death). The results show that there are two functional barriers to endotoxin: - the intestinal barrier, which normally prevents large amounts of toxin from entering the circulation; and RES, which plays a part in detoxifying and eliminating endotoxin which has been absorbed. Application of these findings to the pathogenesis of coli, enterotoxaemia is discussed.