In the central nervous system, type II 5' deiodinase (5'D-II) is highly regulated, as judged by the dramatic changes in enzyme levels observed after abrupt alterations in thyroid status. In this work, the 5'-DII activity has been studied in different situations of experimental hypothyroidism (propylthiouracil, methimazole, thyroidectomy, and low iodine diet), in various brain regions (pituitary, cerebellum, brain stem, hypothalamus, cortex, and whole brain) in adult rats. Propylthiouracil and methimazole significantly increase the activity in all brain regions. These increases are higher in rats treated with methimazole. Thyroidectomy significantly increases the activity in cortex and pituitary. A low iodine diet significantly increases in all brain regions except in the hypothalamus. The concentration of triiodothyronine (T3) studied in the major brain regions remained unchanged. The results obtained show a compensatory mechanism in pituitary and other brain regions in order to maintain the T3 levels in brain tissue.