In housekeeping and many tissue-specific genes, the promoter is embedded in a so-called CpG island. We have compared the available human and mouse DNA sequences with respect to their CpG island properties. While mouse sequences showed a simple gradient distribution of G + C content and CpG densities, man had a distinct peak of sequences with typical CpG island characteristics. Pairwise comparison of 23 orthologous genes revealed that mouse almost always had a less pronounced CpG island than man, or none at all. In both species the requirements for a functional CpG island may be similar in that most DNA regions with a density of six or more CpG per 100 bp remain unmethylated. However, the mouse has apparently experienced more accidental CpG island methylation, suggested by local TpG and CpA excess. We propose that: (1) in mouse the CpG islands do not represent the ancestral state but have been eroded during evolution, and (2) this erosion may be related to the mouse's small body mass and short life-span, allowing for a more relaxed control of gene activity.