To determine the possible effects of thyroid therapy on the course of atherosclerosis, 347 patients (173 males and 174 females) were selected for a five-year study. The atherosclerosis was symptomatic in 132 patients (mean age, 64.5 years), and asymptomatic in 215 (mean age, 54.7). The asymptomatic patients were considered high risks, however, because of the presence of one or more of the following: nonspecific ECG abnormality, arterial hypertension, diabetes, or hypercholesterolemia. Of the total group, approximately 9 per cent (31 of 347) were hypothyroid by laboratory tests; the remainder were euthyroid. All patients were treated with desiccated thyroid in physiological dosage. Substantial clinical improvement was measurable in a significant number of patients in both groups. The mean serum level of total cholesterol was reduced by 22.2 per cent. A more favorable ECG pattern was observed in 14 per cent. Cardiovascular morbidity was less than predicted. Eleven deaths (mean age of patients, 75) occurred during the study; in 10 of these cases there had been one or more symptomatic episodes of atherosclerosis before treatment. The mortality rate was 58 per cent of the expected rate for a matching population as drawn from New Jersey Life Tables, and 44 per cent of the expected rate as drawn from U. S. Life Tables. Thyroid therapy deserves a more extensive trial as a possible means of modifying or preventing the effects of atherosclerosis.