Colonic mucosal cells are known to contain several neuropeptides. The distribution of various peptide-containing cells in the colon and their possible modulation by aging and diet are unknown. We quantitated various peptide-containing cells from male Lobund-Wistar rat colon at 2, 22, 28, 30 and 33 months of age using indirect immunohistochemical techniques for several peptides including: neuropeptide Y, peptide YY, somatostatin, and chromogranin A. Four diets, varying in total calories and fat content, were examined. Serum gastrin was quantified by RIA at 2 and 33 months. Only NPY-, PYY- and SOM-positive cells were found in the colon. The number per crypt of neuropeptide Y-positive (0.55 +/- 0.04 at 2 months vs 0.80 +/- 0.22 at 33 months, P = 0.015) and peptide YY-positive cells increased with age. Staining for somatostatin and chromogranin, a marker for all enterochromaffin (EC) cells, revealed no change with aging. Diet did not influence the numbers of any peptide-containing cell. Serum gastrin was not different between the groups. A specific increase in NPY- and PYY-positive cells occurs in the aged rat colon. The extent to which this change may be related to age-related colonic dysmotility seen in elderly humans is worthy of exploration.