Membrane lipid composition is altered in the brain during the pathogenesis of several age-related neurodegenerative diseases, including Alzheimer's disease. The entorhinal cortex is one of the first regions of the brain to display the neuropathology typical of Alzheimer's disease, yet little is known about the changes that occur in membrane lipids within this brain region during normal aging (i.e., in the absence of dementia). In the present study, the phospholipid composition of mitochondrial and microsomal membranes from human entorhinal cortex was examined for any changes over the adult lifespan (18-98 years). Overall, changes in several molecular phospholipids were seen with age in the entorhinal cortex across both membranes. The proportion of total phosphatidylcholine within the mitochondrial fraction increased within the entorhinal cortex with age, while total mitochondrial phosphatidylethanolamine decreased. Many mitochondrial phosphatidylethanolamines containing docosahexaenoic acid increased with age; however, this did not translate into an overall age-related increase in total mitochondrial docosahexaenoic acid. The most abundant phospholipid present within the human brain, PC 16:0_18:1, also increased with age within the mitochondrial membranes of the entorhinal cortex. When compared to other regions of the brain, the phospholipid composition of the entorhinal cortex remains relatively stable in adults over the lifespan in the absence of dementia.