Abnormalities in DNA synthesis and cell proliferation are characteristic of aged populations of proliferating cells. Cytogenetic analysis of jejunal crypt cells from young and senescent rats indicates that the imbalance in cell production in vivo is associated with an age-dependent increase in metaphase chromosome aberrations. Furthermore, the frequency of these chromosome aberrations is correlated with histologic evidence of cell death. These results demonstrate that the maintenance of genomic integrity is disturbed in the aged small intestine and may explain the age-related increase in the proportion of relatively undifferentiated villus epithelial cells in the small intestine of senescent rats.