To elucidate overall changes in DNA methylation occurring by inappropriate epigenetic control during ageing, we compared fetal bovine fibroblasts and their aged neomycin-resistant versions using bisulfite-PCR technology. Reduction in DNA methylation was observed in euchromatic repeats (18S-rRNA/art2) and promoter regions of single-copy genes (the cytokeratin/beta-lactoglobulin/interleukin-13 genes). Contrastingly, a stable maintenance of DNA methylation was revealed in various heterochromatic sequences (satellite I/II/alphoid and Bov-B). The differential inheritance mode of DNA methylation was confirmed through the analysis of individual neomycin-resistant clones. These global, multi-locus analyses provide evidence on the tendency of differential epigenetic modification between genomic DNA regions during ageing.