Unidentified substances in acetic acid column eluates, obtained in the determination of serum thyroxine by column chromatography with the anion-exchange resin Dowex-1, prevented the direct determination of thyroxine by interference with the iodidecatalyzed ceric-arsenite reaction. Pretreatment of the eluates with Br2 or Cl2 eliminated the interference and permitted the direct assay of thyroxine by the ceric-arsenite system without incineration or wet digestion. Pretreatment with Br2 or Cl2 also significantly enhanced the catalytic activity of thyroxine, rendering its iodine nearly equivalent to inorganic iodide in the ceric-arsenite system. This nonincineration thyroxine assay is significantly more specific than methods that employ wet or dry ashing, because many organic iodine compounds used in diagnosis and therapy are not measured. A comparison of the nonincineration technic with the alkaline dry-ash method on 110 random serums revealed a mean difference of 0.13 µg./100 ml. (X = 4.5 µg./ 100 ml.), with the nonincineration technic yielding the higher result. This difference was found to be statistically significant (p< 0.001).