The effect of the radio-protective agents 2-mercaptoethylamine (MEA) 2-aminoethylisothio-uronium-Br.HBr (AET), and 5-hydroxytryptamine (serotonin) on thyroid activity was studied in nonirradiated and X-irradiated rats. Serotonin appeared to increase whereas MEA or AET decreased I131 uptake by the thyroid and by serum protein-bound iodine. In the X-irradiated rats, serotonin did not markedly increase Il31 uptake. Initially, AET lowered I131 uptake slightly more than MEA, but the effect of MEA wore off more quickly than that of AET. Only in the nonirradiated serum protein-bound I131 samples did the mixture of MEA+AET appear to exert a synergistic effect in lowering I131 uptake.