3H-Pro-Leu-Gly-NH2, a melanocyte-stimulating hormone release inhibiting factor, was injected into 5 healthy men. A plot of the time of the disappearance of radioactivity in plasma wascharacteristic of a multiexponential curve. The half-life of the first component was 1.9 ± 0.06 min and of the second component 15.2 ± 1.5 min. The distribution volume was 20 % of the body weight. One hour after the injection of labeled MIF, 17.2 ± 0.7% of the dose of radioactivity was found in the urine and after 24 h, 25% had been excreted. Extraction of the urine, followed by chromatography on carboxymethyl cellulose and thin layer electrophoresis, showed that over 70% of the radioactivity was associated with the intact molecule while a smaller amount appeared to be either free proline, Pro-Leu-OH, or the deaminated form of the tripeptide. It appears that the main pathway for the clearance of MIF from the human body is excretion of the intact molecule.