In a previous study from this laboratory, chlorine dioxide (ClO2) treated drinking water depressed thyroxine (T4) levels in the African green monkey. The present study again demonstrated a decrease in T4 levels in the same species after 4 wk of oral exposure. However, after 8 wk of treatment T4 levels rebounded to above pretreatment levels, coinciding with an increase in thyroid radioiodide uptake. This T4 rebound phenomenon and increased iodide uptake may be due to a compensatory endocrinological mechanism. In rats, T4 levels dropped during the 8-wk ClO2 treatment period in a dose-dependent manner, and no rebound effect was observed. Iodide uptake values in the rat were not affected. It appears that ClO2 may have an effect on thyroid function in both species.