It was recently demonstrated that treatment with levorotatory thyroxine (T4) plus triiodothyronine (T3) compared with treatment with T4 alone improves psychologic functioning in hypothyroid patients with thyroid cancer or autoimmune thyroiditis. In the present double-blind crossover study, we again compared the effects of combined thyroid replacement vs monotherapy on psychologic function, endocrine function, cardiovascular function, and body composition. The patients were women who were hypothyroid after thyroidectomy for Graves' disease. The substitution of 10 microg of T3 for 50 microg of T4 caused a statistically significant decrease in free T4 concentration but no significant change in T3 or thyroid-stimulating hormone concentration. Symptoms of hypothyroidism and of hyperthyroidism tended to decrease on a standard symptom scale after combined treatment. With combined hormone replacement, mental state tended to improve on some mood scales but not on cognitive tests. We found alterations in left ventricular diastolic function but no change in body composition after the combined treatment regimen. These preliminary findings in a small group of patients with Graves' disease are consistent with earlier findings that thyroid replacement with T4-T3 combination improves mental functioning.