The purpose of this study was to evaluate the prevalence of hypothyroidism in a sample of lithium-treated manic-depressive outpatients who had been under treatment for several years. The sample included 86 patients, 70 females and 16 males, who had been treated for an average of 80 months. One-hundred-and-five blood donors, 58 females and 47 males, aged from 21 to 70 years, served as a reference population for the determinations of serum triiodothyronine (T3), thyroxine (T4), triiodothyronine-resin uptake (T3RU), the free T3 and T4 indices (FT3I and FT4I) and thyroid-stimulating hormone (TSH).Raised TSH levels occurred in 20 patients (23 %), all females, and all but one being over the age of 40 years. This prevalence of 19 cases of hypothyroidism among 56 females over 40 years of age (34 %) contrasted sharply with one single case in the remaining 30 patients (P < 0.001). Highly significant reductions (P < 0.001) of FT3I3I and FT4I were observed in the 20 patients with raised TSH levels, in whom log TSH also correlated very closely with FT3I and FT4I (r=\m=-\0.73and \m=-\0.86,respectively, P <0. 001). The remaining patients had average normal values of T4, FT4I and TSH, but slightly depressed levels of T3 (P < 0.05) and FT3I (P <0.01), possibly reflecting decreased peripheral deiodination of thyroxine.Our data suggest, that cases of hypothyroidism continue to appear as treatment continues. Determination of TSH is recommended at 6 to 12 months intervals in manic-depressive patients undergoing long-term lithium therapy. 759