Although previous studies suggest that in aging animals the small intestine is in a hyperproliferative state, no information is currently available on the influence of age on the proliferation pattern of human small bowel enterocytes. The immunohistochemical expression of the proliferating cell nuclear antigen (PCNA), the villous height to total mucosal thickness ratio and the enterocyte height were evaluated in a panel of duodenal biopsy specimens obtained from 18 subjects aged less and 14 subjects aged more than 65 years. There was a significant positive correlation (P < 0.001) between age in years and percent of positive PCNA enterocytes both at the level of crypts (rs = 0.50) and villi (rs = 0.77). Moreover, the percentage of PCNA+ enterocytes was significantly higher in elderly versus adult subjects, both at the level of villi (6.5 vs 0%; P < 0.001) and of crypts (40.0 vs 23.7%; P < 0.01). No correlation was found between the percentage of PCNA + enterocytes and enterocyte height or villous height to total mucosal thickness ratio. Our results show that PCNA reactivity increases with advancing age both in crypts and villi. This abnormality of the proliferation pattern may explain the coexistence of normal morphology and impaired absorptive function in the elderly.