Dendritic neuropil is a sensitive indicator of the aging process and may exhibit regional cortical variations. The present study examined regional differences and age-related changes in the basilar dendrites/spines of supragranular pyramidal cells in human prefrontal (area 10) and secondary occipital (area 18) cortices. Tissue was obtained from the left hemisphere of 26 neurologically normal individuals ranging in age from 14 to 106 years (M(age) = 57 +/- 22 years; 13 males, 13 females). In tissue prepared by a modified rapid Golgi technique, ten neurons were sampled from each cortical region (N = 520) and were evaluated according to the following parameters: total dendritic length, mean segment length, dendritic segment count, dendritic spine number, and dendritic spine density. The effects of age and Brodmann areas were analyzed with a nested multiple analysis of variance design. Despite considerable interindividual variation, several clear findings emerged: 1) Dendritic systems were significantly larger in area 10 than in area 18 across the sampled life span, presumably because of the more integrative function of area 10 neurons. 2) There was a significant age effect, with a substantial decline in dendritic neuropil from the younger (< or =50 years) group to the older (>50 years) group, especially in spine measures, which decreased almost 50%. 3) Dendritic values were relatively stable after 40 years of age, suggesting that dendritic/spine degeneration in older, relatively healthy individuals may not be an inevitable consequence of the aging process. These findings underscore the importance of life-long commitment to a cognitively invigorating environment.