Although analysis of genome rearrangements was pioneered by Dobzhanskyand Sturtevant 65 years ago, we still know very little about therearrangement events that produced the existing varieties of genomicarchitectures. The genomic sequences of human and mouse provideevidence for a larger number of rearrangements than previouslythought. We describe a new algorithm for constructing synteny blocks,study arrangements of synteny blocks in human and mouse, derive a mostparsimonious human-mouse rearrangement scenario, and provide evidencethat intrachromosomal rearrangements are more frequent thaninterchromosomal. Our analysis is based on the human-mouse breakpointgraph, which reveals related breakpoints and allows one to find a mostparsimonious scenario. We also provide the first evidence that thewidely accepted Nadeau-Taylor model of chromosomal rearrangements mustbe revised, in view of details that were not visible prior to theavailability of high-resolution genomic sequences.Potential recruitment candidate for Bioinformatics