Previous studies have shown that blood concentrations of free thyroxin and basal thyroid-stimulating hormone (TSH) decrease during adult life. Suggested mechanisms include reduced thyroid activity resulting from decreased serum TSH concentrations, impairment of peripheral 5'-deiodinase, and an increase in reverse 3,5,3'-triiodothyronine due to non-thyroidal illness. However, testing of pituitary reserves leads to contradictory results and has infrequently been evaluated in studies.We investigated whether the response of TSH to thyrotropin-releasing hormone (TRH) is preserved during aging. This was tested in a cohort of 387 subjects aged 13 to 100 years in whom thyroid disease was excluded by normal thyroid ultrasound, normal values for free thyroxin, free triiodothyronin, TSH, and negative thyroid peroxidase antibodies.Serum concentrations of free thyroxin remained almost unchanged, whereas free triiodothyronin and TSH levels were lower in older subjects. In addition, the TSH response to TRH was blunted in older subjects, especially in male individuals.There is evidence that the decreased thyroid hormone levels observed in aging are due to lower TSH concentrations, and that lower TSH concentrations may be linked to an impaired pituitary activity.