In recent years, copy number variation (CNV) of DNA segments has become a hot topic in the study of genetic variation, and a large amount of CNVs has been uncovered in human populations. The CNVs involving the smallest units of DNA segments are microsatellite DNAs, and the evolutionary change of microsatellite DNAs is believed to occur mostly by the increase or decrease of one repeat unit at a time in a more or less neutral fashion. If we note that eukaryotic genomes contain millions of microsatellite loci, this pattern of nucleotide change is expected to generate random changes of genome size, that is, genomic drift, and will provide a neutral model of CNV evolution. We therefore investigated the amount of variation of the total number of repeats (TNR) per individual concerned with 145 microsatellite loci in three human populations, Africans, Europeans, and Asians. It was shown that the TNR follows the normal distribution in all three populations and that the extent of variation of TNR is more than 50% greater in Africans than in Europeans and Asians as expected from the hypothesis of African origin of modern humans. If we consider all microsatellite loci in the human genome and compute the variation of the total number of nucleotides involved (TNN), it is possible to study the contribution of microsatellite loci to the genome size variation. This study has shown that the genome sizes of human individuals are affected considerably by genomic drift of microsatellite DNA alone. This pattern of evolution is similar to that of olfactory receptor (OR) genes previously studied in human populations and support the idea that the number of OR genes has evolved in a more or less neutral fashion. However, this conclusion does not necessarily apply to the genomewide CNVs of various DNA segments, and it appears that long variant DNA fragments are deleterious and under purifying selection.