The influence of hypothyroidism in the adult rat on brain biochemistry was investigated. Hypothyroidism was induced in 6-month-old male rats by partial thyroidectomy coupled with the administration of 6-n-propyl-2-thiouracil (0.005%, w/v) in the drinking water. Age-matched euthyroid males served as the controls. Hypothyroidism resulted in brain region-specific changes in certain catabolic enzyme activities. Acid phosphatase activity was reduced in the cerebellum (by 34%) and the medulla (by 38%), whereas alkaline phosphatase activity was decreased in the midbrain (by 37%) and the subcortex (by 49%). A differential response was also observed in the case of aryl sulphatase activity: aryl sulphatase A (myelin-degradative activity) was diminished in the cerebellum (by 56%), whereas aryl sulphatase B remained unchanged in all regions. Acetylcholine esterase activity was reduced in the cerebellum (by 45%), the medulla (by 34%) and the subcortex (by 45%), whereas monoamine oxidase activity was affected in only one region, the cerebellum, where it was increased by (61%). The compromise of myelin and neurotransmitter degradative enzyme activities may place severe restrictions on normal brain function. The vulnerability of the adult rat cerebellum to the effects of thyroidectomy is commensurate with the known clinical signs of cerebellar dysfunction in adult hypothyroid man. These findings raise the possibility of an important role for the thyroid hormones in the mature brain.