The effect of age on layer 1 of area 46 of prefrontal cortex was determined in the cerebral cortices of 15 rhesus monkeys, 13 of which had been behaviorally tested. Five of the monkeys were young (5-7 years of age), three were middle-aged (9-12 years) and seven were old (24-32 years). It was found that with age, layer 1 becomes significantly thinner and the glial limiting membrane becomes thicker. Counts of synapses in layer 1 of seven of these monkeys using the physical disector method on thin sections revealed that compared to young monkeys, there is a 30-60% reduction in the density of synapses per unit volume in old monkeys. This loss of synapses is accompanied by a reduction in the frequency of profiles of postsynaptic dendrites and their spines from the neuropil of layer 1, indicating that some spiny dendrites that belong to the apical dendritic tufts of pyramidal cells are degenerating and being lost with age. Correlation of these morphological changes with the behavioral data shows that there is a significant correlation between the thickness of layer 1 and memory function, as measured by the 2 min delay condition of the delayed non-matching to sample task. Also, there is significant correlation between the numerical density of synapses in layer 1 and three of the behavioral measures used, as well as the Cognitive Impairment Index. Thus, the changes that occur with age in layer 1 provide one possible basis for the age-related cognitive impairment evidenced in monkeys and humans alike.