The level of S-100 protein in rat blood plasma (about 1.4 ng/ml), which was detectable by the present immunoassay method, was markedly increased by a single injection of epinephrine (5 h after injection, 19.7 +/- 5.2 ng/ml). The S-100 protein thus increased was eluted in the same fractions as that of rat brain on butyl-Sepharose 4B column chromatography. The S-100 protein levels were also enhanced moderately by norepinephrine and slightly by isoproterenol, but not by insulin. It is strongly suggested that the increased S-100 protein in blood plasma is derived mainly from the adipose tissue through the effect of catecholamines.