Lithium has been reported to be goitrogenic when used for the treatment of manic-depressive psychosis. To investigate the effects of lithium on iodine metabolism, male Sprague-Dawley rats were placed on a low iodine (LID) or normal iodine diet (NID) containing enough Li₂CO₃ to give serum lithium levels of 0.23-0.86 mEq/liter (human therapeutic range is 0.6-1.6 mEq/liter). The following effects were noted with lithium treatment: (a) thyroid weight increased concomitant with a slowing of thyroidal iodine release; (b) the ability to concentrate iodide was increased only after goiters were established; (c) on the LID, ¹³¹I uptake was elevated throughout all phases of treatment, even when the release rate was normal; (d) iodine organification was unaffected but the proportion of ¹³¹I present as iodothyronines was decreased; (e) the thyroidal ¹²⁷I content was increased; (f) despite these changes, the serum PBI remained normal as did the thyroxine turnover rate; and (g) thyrotropin (TSH) levels in serum were the same as controls except for a slight elevation early in the course of treatment; TSH levels did not correlate with goitrogenesis.