Sodium salicylate is antipyretic in experimental endotoxin fevers in rabbits but is not significantly antipyretic in fevers induced by leucocytic pyrogen. The in vitro production of pyrogen by leucocytes is significantly decreased by salicylate. The accumulated evidence suggests that in rabbits the antipyretic effect of salicylate is not central on the hypothalamus but is peripheral on the leucocyte to inhibit formation or release of its pyrogen.