The requirement for DNA sequence homology in generalized genetic recombination is greatly relaxed in bacterial mutL, mutS and mutH mutants deficient in mismatch repair. In such mutants, intergeneric recombination occurs efficiently between Escherichia coli and Salmonella typhimurium, which are approximately 20% divergent in DNA sequence. This finding has implications for speciation, for regulating recombination between diverged repeated sequences, and for hitherto difficult interspecies hybridizations.