Perchlorate interferes with iodide accumulation in the thyroid resulting in reduced thyroidal hormone synthesis. The objective of this project was to conduct a series of experiments to investigate the role of perchlorate on the uptake of iodide in the thyroid and its effects on the synthesis of thyroid hormones. A time course study with perchlorate (single iv dose) was performed to investigate its kinetic behavior in the adult male rat. Rats were injected with 0, 0.01, 0.11 and 3 mg perchlorate/kg via tail vein, challenged with 1251 with carrier at 2 h post dosing, and euthanized at predetermined time points. Three groups (n=6 per group) of 1-, 5-, and 14-day drinking water studies were performed at different levels of perchlorate (0, 1, 3 and 10 mg/kg). At the end of exposure, rats were challenged once by tail vein injection with 1251 with carrier. Dose-related inhibition of thyroid iodide uptake after a single iv dose of perchlorate, and both dose- and time- dependent changes in inhibition of thyroid iodide uptake were observed in drinking water studies. In both the single dose and drinking water studies, TSH and free T4 levels were elevated with T4 levels decreased. Serum T3 levels in drinking water studies remained unchanged in all dosing groups.