The effects of carrageenin on the antipyretic activity and the plasma concentration of drugs after oral administration of aspirin-phenacetin preparation in rats were investigated. 1) The reproducible hyperthermic pattern was obtained by administration of carrageenin in rats. There were no remarkable changes in liver function of febrile rats induced by carrageenin. The rectal temperature was rapidly decreased by oral administration of aspirin-phenacetin preparation, but the rectal temperature of normal rats was not influenced. 2) In carrageenin febrile rats, plasma concentrations of aspirin, phenacetin and their metabolites, salicylic acid and acetaminophen, were lower than those in normal rats. It was suggested that these results were due to depression of gastric emptying rate and propulsive rate of intestine. 3) Fatty acids of lipid in the serum from febrile rats decreased and those in the brain increased. After administation of aspirin-phenacetin preparation in febrile rats, the fatty acid composition of lipid in the brain was altered and the amounts of oleic acid and arachidonic acid incresed. 4) The variations in serum electrolytes were observed in carrageenin febrile rats. It was suggested that these variations were related to a decrease in bile flow, a rise in blood sugar value and a decrease in aspirin esterase activity.