Thirty seconds after an intravenous injection of 0.5 ml of 2.5 × 10−6 M [3H]thyrotropin-releasing hormone (TRH) to male rats, the radioactivity was distributed in an apparent volume of 134 ml, thus reflecting its rapid disappearance from the blood. The pattern of plasma radioactivity after intravenous injection of [3H]TRH could be represented by the sum of three exponentials, suggesting a three-compartment model of plasma disappearance of radioactivity. The half-life of TRH and of its metabolites calculated from the first exponential curve was 2.2 min. Thin-layer electrophoresis of methanol extracts of plasma collected 1, 7, 20, and 30 min after injection of [3H]TRH showed that the neurohormone was transformed into TRH-free acid in proportions of 58, 58, 52, and 47%, respectively. The first 60 min seemed to be the most important period for elimination of the hormone and its metabolites by the kidney. In fact, 60 min after injection, 38% of the total radioactivity was found in the bladder. At 2, 15, and 30 min after injection of [3H]TRH, high accumulation of radioactivity occurred in kidneys, pineal gland, and anterior and posterior (including intermediate) lobes of the pituitary. High levels of radioactivity were seen in kidneys and anterior pituitary gland at all time intervals studied.