To facilitate comparison of the genome maps of Mycobacterium tuberculosis and M. leprae, sequence data from the M. leprae sequencing project were used to design primers suitable for the amplification of short segments from conserved genes by the polymerase chain reaction. In most cases, both organisms yielded products of identical size that were then used as probes for a comparative genomic walk. The hybridization data often, but not always, revealed a similar organization of various regions of both genomes. This approach should be useful for systematic comparisons of (myco)bacterial genomes.