The purpose of this study was to investigate the effects of hyper- and hypothyroidism on thyroid hormone concentrations and deiodinase activities in nine regions of the rat brain. Four weeks of treatment with 75 μg thyroxine (T₄)/kg body wt induced a two- to threefold increase in T₄ levels in all of these brain regions, whereas the 3,5,3′-triiodothyronine (T₃) concentrations were reduced in five brain regions and remained unchanged in four. Even after 8 wk treatment with 300 μg T₄/kg, the T₃ concentrations remained normal in cortical areas, the hippocampus and amygdala, and were elevated only in areas in which inner-ring deiodinase activity was low or absent, and in the hypothalamus. At the subcellular level, nuclear concentrations of T₃ were diminished in hypothyroidism but remained unaltered in hyperthyroidism in all areas except the hypothalamus, where they were enhanced. Cortical mitochondrial succinate dehydrogenase activity was reduced in both hypo- and hyperthyroidism in spite of normal T₃ concentrations in hyperthyroid animals. The results show that nuclear T₃ concentrations fall in hypothyroidism but do not change during severe hyperthyroidism in any brain region except the hypothalamus. Further research is thus needed to clarify the mechanisms mediating the numerous biochemical and psychological effects of hyperthyroidism.