Homologous recombination impacts profoundly on the biology of Neisseria gonorrhoeae either by shuffling gene sequences that encode surface antigens, or by disseminating variant alleles via horizontal transmission in vivo. Consequently, large variant populations exist in nature, which make therapeutic intervention more difficult and impairs the efficacy of many vaccine candidates. The goal of these studies is to define; I) molecular mechanisms involved in the rearrangement of the gonococcal chromosome (specifically, recombination at the pilE locus); ii) parameters that may exist in intercellular exchange of chromosomal DNAs; and iii) genetic techniques that may be applied for novel therapeutic interventions.