No difference was found between warfarin‐treated and untreated rabbits with regard to the pyrogenic response to Salmonella typhi endotoxin by comparison of the contours of the fever curves, the fever indices, the latent periods and the various temperatures (1‐hr, 3‐hr and maximum temperature). A constant low coagulation activity is therefore of no consequence to the pyrogenic reaction, provided the endotoxin is intravenously administered. This strongly indicates that the endotoxin‐induced alterations of the blood coagulability have no decisive influence on the pyrogenic response. The dose‐response relationship was more reliably determined in tolerant than in nontolerant rabbits. The fever index seemed to be the most reliable of the response parameters in discriminating between doses. The relation between the blood coagulability and the R.E.S. function is discussed.

The primary elimination from circulating blood of intravenously administered endotoxin, and the primary distribution of the phagocytised endotoxin have been compared in warfarinpretreated and untreated rabbits. The results show that the elimination rate of endotoxin is significantly higher in warfarin‐treated rabbits than in untreated. The difference is, however, small, and does not reflect a significant difference in the organ distribution although the amounts of endotoxin in the organs are somewhat higher in the warfarin‐treated animals. Twenty min after injection about 75 per cent of the injected endotoxin has been eliminated from circulation, and about 50 per cent of the injected dose is located to the liver. The highest amount of endotoxin per g tissue is, however, found in the lungs. Twenty min after injection the same percentage, about 90, of circulating endotoxin was in both groups located to the plasma phase. The fact that the clearance rate of endotoxin in warfarin‐treated rabbits in higher than in untreated rabbits is thought to be due to the existence of a competitive phagocytosis of endotoxin and fibrin clots and not to a changed endotoxinplatelet interaction.

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Warfarin‐treated and untreated rabbits were immunized by a series of daily injections of Salmonella typhi endotoxin. The sera were tested by bacterial agglutination, indirect hemag‐glutination, indirect hemolysis and precipitation. Analysis of variance showed no difference in the quantity of antibodies formed in warfarin‐treated and untreated rabbits. The antibodies were shown to be exclusively gammaM‐globulins. It is concluded that a constant low coagulation activity, such as that achieved by warfarin treatment, is of no consequence to antibody formation, provided the endotoxin is intravenously administered. This may indicate that the endotoxin‐induced alterations of coagulability do not affect any phase of antibody formation. No correlation seemed to exist between the antibody levels and the pyrogenic response, as measured in the same rabbits.

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