Converging evidence suggests a possible link between thyroid state and Alzheimer's disease (AD), including a higher probability of dementia in individuals with higher TSH levels and a two-fold risk of AD in patients with hypothyroidism. Thyroid hormones modulate factors associated with AD, including amyloid precursor protein expression in the brain, suggesting a possible role for thyroid hormone in AD pathology. The present study is the first to directly evaluate brain thyroid hormone levels in AD. Triiodothyronine (T(3)) and thyroxine (T(4)) levels were measured with radioimmunoassay (RIA) in post-mortem samples of prefrontal cortex of patients with pathologically confirmed AD, including Braak stage I-II (n=8), Braak stage V-VI (n=8), and controls without any primary neurological disease (n=8). T(4) levels did not differ between groups. T(3) levels were significantly lower in Braak stage V-VI brains relative to controls, but there was no statistically significant difference between T(3) levels in Braak stage I-II versus controls. Results suggest that the conversion of T(4) to T(3) may be affected in advanced AD, perhaps due to alterations in deiodinase activity. Reduced conversion of T(4) to T(3) in AD may be associated with both AD pathology and the clinical presentation of dementia.