Mutational rates are known to be variable along the mammalian genome but the extent of this non-random fluctuation and their causes are less well understood. Using 5509 human and mouse orthologous genes with known chromosome positions, it is shown here that there are extreme differences in synonymous evolutionary rates between different human chromosomes when distances are measured using maximum-likelihood techniques. In particular, the average synonymous rate of genes located in human chromosome 19 is extremely high (K(s) = 1.243 substitutions/site) compared with the average of all genes (K(s) = 0.729), and significantly different from all other human chromosomes. When genes are sorted according to mouse chromosomes no such large differences are found. Strikingly, almost all genes of human chromosome 19 have very high GC content in humans but not in the mouse orthologs. More generally, correlation analysis shows that genes with very high GC content in humans have experienced the highest synonymous divergencies from the mouse. It is likely that, in such genes, the known relaxation of the isochore structure in rodents has caused an increased accumulation of synonymous substitutions in the mouse lineage, whereas the regions with the highest GC content in the human genome are accordingly maintained by a strong selective pressure.