The glycoprotein reelin has been implicated in both memory-related synaptic plasticity and Alzheimer's disease pathogenesis. Aged rats with memory impairment display decreased reelin expression in layer II of the entorhinal cortex (EC) relative to memory-intact subjects, and here we tested whether this effect extends to the primate brain. Seven young adult (8-10 years) and 14 aged (27-38 years) rhesus monkeys (Macaca mulatta) were examined, including 7 old animals classified as impaired based on their scores from a delayed nonmatching-to-sample recognition memory test. Histological sections spanning the rostrocaudal extent of the intermediate and caudal divisions of EC were processed by immunohistochemistry and the total number of reelin-positive neurons in layer II was estimated using design-based stereological techniques. The main finding was that the number of reelin-expressing neurons in EC layer II is decreased selectively in aged monkeys with memory deficits relative to young adult and aged subjects with intact memory. The results add to evidence implicating EC-hippocampal integrity in neurocognitive aging, and they suggest that disrupted reelin signaling may be among the mechanisms that mediate the associated vulnerability of this circuitry in Alzheimer's disease.