Although bacterial species display wide variation in their overall GC contents, the genes within a particular species' genome are relatively similar in base composition. As a result, sequences that are novel to a bacterial genome—i.e., DNA introduced through recent horizontal transfer—often bear unusual sequence characteristics and can be distinguished from ancestral DNA. At the time of introgression, horizontally transferred genes reflect the base composition of the donor genome; but, over time, these sequences will ameliorate to reflect the DNA composition of the new genome because the introgressed genes are subject to the same mutational processes affecting all genes in the recipient genome. This process of amelioration is evident in a large group of genes involved in host-cell invasion by enteric bacteria and can be modeled to predict the amount of time required after transfer for foreign DNA to resemble native DNA. Furthermore, models of amelioration can be used to estimate the time of introgression of foreign genes in a chromosome. Applying this approach to a 1.43-megabase continuous sequence, we have calculated that the entire Escherichia coli chromosome contains more than 600 kb of horizontally transferred, protein-coding DNA. Estimates of amelioration times indicate that this DNA has accumulated at a rate of 31 kb per million years, which is on the order of the amount of variant DNA introduced by point mutations. This rate predicts that the E. coli and Salmonella enterica lineages have each gained and lost more than 3 megabases of novel DNA since their divergence.