The mean DNA content per cell and heterogeneity of cell populations with respect to DNA content were measured in samples of peripheral blood mononuclear cells from donors of different ages. Nearly all of the cells in these populations are found in the G1Q phase of the cell cycle. While the mean DNA content was the same for all age groups, a significant increase in intercellular variability, reflected by an increase in coefficient of variation of the mean, was observed in the group of subjects between 67 and 83 years of age in comparison with the group of donors between 20 and 30 years of age. The difference was observed regardless of whether cells were stained with acridine orange or propidium iodide, and under conditions where the intercellular variability cannot be attributed to differences in chromatin structure or quantity of mitochondrial DNA. Increasing cell heterogeneity may reflect the age associated deterioration of the fidelity of DNA replication and/or repair and provide a quantitative marker of the accumulated defects in the DNA of a cell population. The observed changes may be responsible for the decline in immune function with age.