Concerns have been raised over the use of iodine for disinfecting drinking water on extended space flights. Most fears revolve around effects of iodide on thyroid function. Iodine (I2) is the form used in drinking-water disinfection. Risk assessments have treated the various forms of iodine as if they were toxicologically equivalent. Recent experiments conducted in rats found that administration of iodine as I- (iodide) versus I2 had opposite effects on plasma thyroid hormone levels. I2-treated animals displayed elevated thyroxine (T4) and thyroxine/triiodothyronine (T4/T3) ratios, whereas those treated with I- displayed no change or reduced plasma concentrations of T4 at concentrations in drinking water of 30 or 100 mg/L. The study herein was designed to assess whether similar effects would be seen in humans as were observed in rats. A 14-d repeated-dose study utilizing total doses of iodine in the two forms at either 0.3 or 1 mg/kg body weight was conducted with 33 male volunteers. Thyroid hormones evaluated included T4, T3, and thyroid-stimulating hormone (TSH). TSH was significantly increased by the high dose of both I and I-2, as compared to the control. Decreases in T were observed with dose schedules with I-4 and I2, but none were statistically significant compared to each other, or compared to the control. This human experiment failed to confirm the differential effect of I2 on maintenance of serum T4 concentrations relative to the effect of I- that was observed in prior experiments in rats. However, based on the elevations in TSH, there should be some concern over the potential impacts of chronic consumption of iodine in drinking water.