After the injection of 14C-labeled TRH into normal male rats, radioactivity disappeared rapidly from the circulation. The half life of 14C-TRH was found to be 4.16 min; however, the true half life of TRH may be masked, since TRH is rapidly inactivated in the blood to compounds having similar chemical structures and probably similar half lives. Chromatography of methanol extracts of plasma samples taken at 1, 2, and 6 min revealed that some of the radioactivity had the same Rf value as that of TRH, while other areas corresponded to the free acid of TRH (pyro-glu-his-pro-OH), glu-his-pro, and his-pro-NH2. The mean volume of distribution of TRH in our studies was 18.5% of the body weight. Approximately 25% of the radioactivity was excreted into the urine within 60 min after the intravenous injection of 1 µCi of 14C-TRH. Urinary radioactive metabolites appeared to have the same electrophoretic mobilities as TRH and the free acid of TRH.