BACKGROUND: Instability in the organization and expression of the genetic material has been hypothesized as the basic mechanism of ageing. OBJECTIVE: To quantify the effect of ageing on chromosomal damage as measured by spontaneous micronuclei (MN) frequency in peripheral blood lymphocytes. METHOD: Analysis of a large population sample from two laboratories applying the cytokinesis-block technique and a third using traditional interphase analysis. The age-related effect on baseline level of micronuclei frequency and on cell proliferation measures was further investigated in a study of peripheral blood samples from healthy subjects. RESULTS: There was an increase of MN frequency with age. The regression lines showed a positive slope and were statistically significant (P< 0.01) with a steeper trend for cytochalasin B-treated samples. An inverse correlation with age was detected for the percentage of binucleated cells in laboratories using cytochalasin B. This study confirms the increase of basal level of MN with age. A decrease by age in proliferation efficiency measured by the percentage of binucleated cells suggests an interference of age-related factors on cell division. CONCLUSION: There is an increase in MN frequency with increasing age.