In a previous study from this laboratory, chlorine dioxide (ClO ₂ ) treated drinking water depressed thyroxine (T ₄ ) levels in the African green monkey. The present study again demonstrated a decrease in T ₄ levels in the same species after 4 wk of oral exposure. However, after 8 wk of treatment T ₄ levels rebounded to above pretreatment levels, coinciding with an increase in thyroid radioiodide uptake. This T ₄ rebound phenomenon and increased iodide uptake may be due to a compensatory endocrinological mechanism. In rats, T ₄ levels dropped during the 8‐wk ClO ₂ 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 ClO ₂ may have an effect on thyroid function in both species.