Hypothyroidism may occur more commonly in patients with end-stage renal disease (ESRD) than in the general population. The signs and symptoms of both hypothyroidism and uremia may be similar. To evaluate the usefulness of clinical and routine laboratory findings in the diagnosis of hypothyroidism in patients with ESRD, we compared 6 patients with documented primary hypothyroidism who had serum thyrotrophin (TSH) levels above 20 μU/ml with 12 euthyroid patients. The euthyroid patients were divided into two groups. The first was matched with the hypothyroid patients for age, renal disease and duration of dialysis, while the second group was matched for serum total thyroxine and free T4 index values. Serum TSH levels were normal ( < 10 μU/ml) in both of these latter groups. There were no significant differences in the clinical manifestations among the three groups of patients, except for hoarseness of voice which was significantly more common in the hypothyroid uremic patients (p = 0.03). No significant differences were noted on electrocardiogram, physical examination, chest x-ray or echocardiography. Routine laboratory values were not different. Therapy of the uremic hypothyroid patients with L-thyroxine was associated with improvement or resolution of many of the symptoms and signs of hypothyroidism that otherwise would have been attributed to the uremic state. Our results indicate that the diagnosis of hypothyroidism in uremic patients cannot be made by clinical or routine laboratory values and rests on the presence of an overtly elevated serum TSH concentration. Thus, routine measurement of serum TSH levels may be warranted in all patients with ESRD who have reduced total T4 or free T4 index values to insure accurate diagnosis and allow institution of specific therap