We treated 26 hypothyroid women - 11 with autoimmune thyroiditis and 15 who had been treated for thyroid cancer - with their usual dose of thyroxine (T4) or with a regimen in which 50 &mgr;g of T4 had been replaced by 12.5 &mgr;g of triiodothyronine (T3). Patients were first randomly assigned to one regimen for 5 wk and then to a second regimen for an additional 5 wk. The substitution of T3 for a portion of T4 caused expected changes in concentrations of thyroid hormones and thyroid-stimulating hormone (TSH). After combined hormone treatment there were clear improvements in both cognition and mood, the latter changes being greater. The patients who had been treated for thyroid cancer showed more mental improvement than the women with autoimmune thyroiditis, perhaps because they were more dependent on exogenous hormone. Some mood improvements correlated positively with changes in TSH while others correlated negatively with changes in free T4.