The sucutaneous administration of small doses of L-thyroxine sodium (a total of 2 mg in 90 divided doses) over a period of 200 days in middle age had no significant effect on the life duration of the male rat. The mortality rate was increased during treatment, but was diminished in the post-treatment period. Small doses of thyroxine failed to stimulate growth in the intact middle aged rat. Large doses of thyroxine inhibited growth and reduced the body weight. The administration of moderately large doses of L-thyroxine sodium (a total of 9 mg in 90 divided doses) over a period of 200 days in middle age, produced an average loss of 40 g in body weight during treatment. The duration of growth was shortened by 80 days and the life duration reduced by 50 days as the result of this treatment. The mortality rate was increased only during the period of treatment. During treatment with both small and large doses of thyroxine in middle age, statistically significant increases occurred in the consumption of food and water, in the production of feces and urine, in the excretion of protein, non-protein nitrogen, uric acid, phosphate and chloride, and in heart rate. These values returned to normal when treatment was discontinued. The only significant change observed in the post-treatment period in old age, was an abnormal elevation of the blood hemoglobin level in rats treated with large doses of thyroxine. The raised hemoglobin level was probably related to an increased frequency and severity of lung disease in these animals.