L-Carnitine and acetyl-L-carnitine facilitate mitochondrial beta-oxidation of fatty acids. In the brain, they may also have a role in acetylcholine synthesis. Carnitine acetyltransferase catalyzes the interchange between L-carnitine and acetyl-L-carnitine. Recently, acetyl-L-carnitine was reported to have a beneficial effect in patients with Alzheimer's disease. We therefore assessed carnitine acetyl-transferase activity in selected brain regions and in isolated cerebral microvessels obtained at autopsy from patients with Alzheimer's disease and from age-matched control subjects. We found a 25 to 40% decrease in carnitine acetyltransferase activity in patients with Alzheimer's disease, which attained statistical significance in most brain regions and in cerebral microvessels. These findings document another neurochemical abnormality in patients with Alzheimer's disease and provide a rationale for the use of acetyl-L-carnitine in the treatment of patients with Alzheimer's disease.