In experiments designed to elucidate the mechanism by which tolerance to bacterial pyrogens is developed, the following observations were made:

1. Animals whose febrile reactions to bacterial pyrogens were markedly diminished, as a result of repeated injections, showed increases in response following R-E blockade.

2. Pyrogenic substances disappeared from the circulating blood more rapidly in rabbits rendered pyrogen-tolerant than in normal animals. Lack of specificity was shown by the fact that rabbits previously injected with Eberthella typhosa bacterial vaccine were able to remove the pyrogens of Serratia marcescens and Pseudomonas aeruginosa from their blood more rapidly than normal animals.

3. R-E blockade-retarded the speed of disappearance of pyrogens from the circulating blood of animals which had been rendered relatively tolerant by previous injections of these substances.

A possible mechanism for the development of unresponsiveness to bacterial pyrogens is suggested.

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