Thirty-six patients with normal thyroid function and elevated serum cholesterol levels were treated with dextro-isomers of triiodothyronine (D-T3) or thyroxine (D-T4). Eleven patients were treated with D-T3 at gradually increasing doses up to a maximum of 1.5 mg daily, eight being treated for 12 months. Serum cholesterol levels were decreased significantly from control values at dose levels of 0.2 mg or more, clinically significant reductions (25% or more from control values) were obtained in 7 patients. Upon discontinuation of treatment, relapse was prompt. Seven patients were retreated with comparable doses of D-T4 over briefer periods; responses were virtually identical to those from D-T3. Twelve additional patients were treated with D-T4 and 13 with D-T3 using comparable treatment programs. Serum cholesterol levels were significantly reduced from control values at most dose levels for both compounds. Seven of 12 patients on D-T4 and 3 of 13 on D-T3 attained a clinically significant reduction. Serum phospholipids declined to a slightly lesser extent than did serum cholesterol; total lipids were proportionately less reduced, suggesting little effect on serum triglyceride levels. Both drugs caused weight loss, appreciable only in the higher ranges of dosage (2mg daily for D-T3 and 8 mg daily for D-T4); reduction in serum cholesterol levels proceeded more rapidly at lower doses. One patient showed equivocal signs of hypermetabolism while on 8 mg daily of D-T4. Two patients, both on D-T3, developed paroxysmal atrial fibrillation. Six patients developed supraventricular premature contractions, five on D-T4. One patient died suddenly and unexpectedly while on D-T3; he had an old myocardial infarct but no new lesion on post-mortem examination. Another patient had a mild cerebral thrombosis while on D-T4. Protein-bound iodine values increased during treatment with both drugs, to a greater extent with D-T4; 24 -hour uptake of I-131 was reduced. Both these effects were attributed to exogenous organic iodine. Sodium d-thyroxine (D-T4), which will be available for clinical use, merits a trial in the type of patients reported in the present study as well as replacement therapy for hypo-thyroid patients with elevated cholesterol levels and coronary arteriosclerosis.