About 2% of the genome of Mycobacterium leprae is composed of repetitive DNA. There are more than 26 extinct IS elements together with four families of dispersed repeats, present in five copies or more, RLEP (37 copies), REPLEP (15 copies), LEPREP (eight copies), and LEPRPT (five copies). Although there is no sequence similarity to known transposable elements, RLEP occurs predominantly at the 3'-end of genes and, in several cases, within pseudogenes, suggesting that it was capable of dissemination. Strikingly, on comparison of the genome sequences of M. leprae and the closely related tubercle bacillus, Mycobacterium tuberculosis H37Rv, many of these repetitive sequences were found at sites of discontinuity in gene order. Evidence is presented that loss of synteny, inversion and genome downsizing may have resulted from recombination between dispersed copies of these repetitive elements.