Peroxidase, H2O2, and a halide form a powerful antimicrobial system in phagocytes and tissue fluids, and certain microorganisms can serve as the source of H2O2 for this system. H2O2-generating Lactobacillus acidophilus (LB+) is present in the vagina of most normal women and peroxidase has been detected in vaginal fluid. LB+ at high concentration is viricidal to HIV-1, and, at levels where LB+ is ineffective alone, the addition of peroxidase (myeloperoxidase, eosinophil peroxidase) and a halide (chloride, iodide, bromide, thiocyanate) restore viricidal activity. LB+ can be replaced by H2O2, but not by non-H2O2-producing LB, and viricidal activity is inhibited by azide and catalase. The survival of HIV in the female genital tract and thus the likelihood of transmission may be influenced by the activity of the LB(+)-peroxidase-halide system in the vagina.