1. This paper studies the effect of thyroid status on 5'-D activity in pineal gland, Harderian gland, brown adipose tissue (BAT), pituitary gland, brain frontal cortex (BFC), and cerebellum. 2. Hypothyroidism clearly increased diurnal 5'-D activity in Harderian gland, BAT, pituitary gland, BFC, and cerebellum. In pineal gland, diurnal values of 5'-D activity were not affected by hypothyroidism. 3. Hypothyroidism in adult rats clearly enhanced nocturnal increase of 5'-D activity in pineal and Harderian gland. Congenital hypothyroidism also enhanced the nocturnal increase of 5'-D activity in pineal gland. 4. Hyperthyroidism inhibited 5'-D activity in pituitary gland, BFC, and cerebellum. A small inhibition, although significant, was found in BAT. 5. In pineal and Harderian gland, hyperthyroidism did not inhibit either the basal diurnal values of the enzyme or the nocturnal increase of its activity. 6. Results suggest that, in tissues where 5'D-activity is regulated by adrenergic mechanisms, mostly pineal gland and Harderian gland, the enzyme activity is independent of serum T4 concentrations during hyperthyroidism.