Concerns have been expressed over the use of iodine for disinfecting drinking water on Space Station Freedom. Most of these fears revolve around effects of iodide on thyroid function. However, little attention has been paid to how the chemical form of iodine influences its toxicology. In particular, iodine (I2) is the form used in drinking water disinfection. Previous evaluations have not taken the differing reactivity of iodine into account. The present paper summarizes the results of experiments designed to determine whether iodine ingestion can be considered toxicologically equivalent to identical doses of iodide.Studies ranging from a single dose to repeated doses of iodine and iodide given to Sprague-Dawley rats for as long as 100 days have shown that these two forms of iodine have opposite effects on the concentrations of thyroid hormones in blood. As predicted from the literature, iodide tended to decrease (difference was not statistically significant at P = 0.05 by ANOVA) circulating levels of thyroxine (T4) and increased the size of the thyroid gland. Conversely, iodine significantly increased the concentrations of T4, tended to decrease triiodothyronine (T3) levels and did not increase the weight of the thyroid gland. The most consistent observation with iodine was a significant increase in the T4/T3 ratio.Subsequent experiments have shown that this effect comes about by reaction of iodine with metabolites of thyroid hormone in the intestine. This conclusion is supported by the following observations: 1) Within 2 hours after administration of increasing doses of iodine by gavage, there is a dose-related increase in plasma concentrations of T4 that is mirrored by a decrease in plasma concentrations of T3. 2) Iodine reacts with monoiodothyronine, diiodothryonine and T3 to form T4 in vitro. 3) Iodine reacts with substances present in a wash of the upper segment of the rat small intestine to form T4. These effects are not produced by equivalent doses of iodide.