SUMMARY 1. Para-amino-salicylic acid (PAS sodium salt) given to rats under the experimental conditions described produces a fall of radio-iodine uptake to 10% of the control value at the end of 16 days. After 30 days this low level is unchanged. 2. Oxygen consumption falls gradually to 12% below the control value at the end of 30 days' treatment with PAS. 3. Thyroxine with PAS abolishes the fall in oxygen consumption and raises the radio-iodine uptake slightly above that given with PAS alone. 4. Methyl thiouracil with PAS does not depress the oxygen consumption level below that obtained with PAS alone. The radio-iodine uptake is raised slightly above that found with PAS. 5. After 15 weeks' administration of PAS radio-iodine uptake is more than double that of the control value. 6. The rise in radio-iodine uptake when thyroxine and methyl thiouracil are given with PAS and when PAS treatment is prolonged, is accompanied by structural changes in the thyroid gland indicative of an increased output of thyrotrophic hormone. 7. After 29 weeks' treatment with PAS signs of exhaustion of the thyroid gland appear. Complete degeneration of the follicular epithelium was observed in some animals at this time. 8. The structural changes in the gland are reversible even after 25 weeks' treatment with PAS at a dose level of 1 mg/g body weight/day.