A B S T R A C T Splenectomy markedly impaired the production of circulating anti-endotoxin antibodies during the initial 10 days after i.v. administration of a Boivin preparation of Escherichia coli endotoxin (ET) lated to fall between 1/10 and 1/100 of those used in the splenectomized subjects. The impairment of latephase pyrogenic tolerance after splenectomy appeared to be the result of the concomitant suppression of antiendotoxin antibody production rather than the loss of splenic reticuloendothelium required to clear and inactivate the ET. This was evidenced by: (a) the significant retardation in appearance of humoral factors in the splenectomized rabbits capable of transferring high levels of specific tolerance; (b) the inability to impair the late phase of tolerance in human volunteers with intact spleens until the immunizing doses of endotoxin were reduced to levels that virtually eliminated circulating anti-endotoxin antibody production; (c) the unimpaired development of tolerance in partially hepatectomized rabbits lacking more functional reticuloendothelium than splenectomized animals, but capable of normal anti-endotoxin antibody synthesis.

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