Primate genomic sequence comparisons are becoming increasingly useful for elucidating the evolutionary history and organization of our own genome. Such studies are particularly informative within human pericentromeric regions--areas of particularly rapid change in genomic structure. Here, we present a systematic analysis of the evolutionary history of one approximately 700-kb region of 2p11, including the first autosomal transition from pericentromeric sequence to higher-order alpha-satellite DNA. We show that this region is composed of segmental duplications corresponding to 14 ancestral segments ranging in size from 4 kb to approximately 115 kb. These duplicons show 94%-98.5% sequence identity to their ancestral loci. Comparative FISH and phylogenetic analysis indicate that these duplicons are differentially distributed in human, chimpanzee, and gorilla genomes, whereas baboon has a single putative ancestral locus for all but one of the duplications. Our analysis supports a model where duplicative transposition events occurred during a narrow window of evolution after the separation of the human/ape lineage from the Old World monkeys (10-20 million years ago). Although dramatic secondary dispersal events occurred during the radiation of the human, chimpanzee, and gorilla lineages, duplicative transposition seeding events of new material to this particular pericentromeric region abruptly ceased after this time period. The multiplicity of initial duplicative transpositions prior to the separation of humans and great-apes suggests a punctuated model for the formation of highly duplicated pericentromeric regions within the human genome. The data further indicate that factors other than sequence are important determinants for such bursts of duplicative transposition from the euchromatin to pericentromeric regions.