Exposure to high levels of iodide in Cangzhou, Shandong Province, China has been associated with increased incidence of thyroid disease; however, whether fluoride can affect the thyroid remains controversial. To investigate the effects of excess fluoride, we evaluated thyroid gland structure and function in rats exposed to fluoride and iodide, either alone or in combination. Five-week-old Wistar rats (n = 160 total) were randomly divided into eight groups: three groups that were given excess fluoride (15, 30, or 60 ppm F); one group given excess iodide (1200 ?g/L I); three groups given excess iodide plus fluoride (1200 ?g/L I plus 15, 30, or 60 ppm F); and one control group. The serum concentrations of the thyroid hormones TT3 and TT4 on day 150 were significantly reduced for certain fluoride groups; however, no significant differences were observed in concentrations for the pituitary hormone TSH among any groups. Hematoxylin and eosin staining revealed that iodide causes an increase in the areas of the colloid lumens and a decrease in the diameters of epithelial cells and nuclei; however, fluoride causes an increase in nuclear diameters. The damage to follicular epithelial cells upon fluoride or iodide treatment was easily observed by transmission electron microscopy, but the effects were most dramatic upon treatment with both fluoride and iodide. These results suggest that iodide causes the most damage but that fluoride can promote specific changes in the function and morphology of the thyroid, either alone or in combination with iodide.