Thyroid function was investigated in 100 manic-depressive patients. Goiter was more common in patients treated with lithium for 1-5 years (44%) or more than 10 years (50%) than in patients who never received lithium (16%). Smoking contributed significantly to thyroid size and goiter. In nonsmoking patients, ultrasonically determined thyroid volume was significantly related to treatment duration. The mechanism behind this increased thyroid volume is unclear, as most patients had normal serum thyrotropin levels and no thyroid autoimmunity. Subclinical or overt hypothyroidism was found in 4% and 21% of patients treated for 1-5 and more than 10 years, respectively. Since few hypothyroid patients had autoimmunity or goiter, lithium may affect the thyroid gland directly.