ObjectivesTo identify a substance found in female genital tract secretions that enhances HIV expression in infected cells.DesignCervico-vaginal lavages (CVL), collected in sterile normal saline, were fractionated and tested for HIV-inducing activity using HIV-infected monocytes.MethodsTo purify the component(s) of CVL that enhance HIV production, Mono-Q ion exchange chromatography followed by Superose-12 molecular sieve analysis, and SDS–PAGE were performed. The purified protein was identified by amino acid sequence analysis.ResultsSDS–PAGE of bioactive fractions showed a 14 kDa polypeptide band. Amino acid sequence analysis of selected peptides from the 14 kDa band showed 100% homology with the myeloid-related protein (MRP)-8, an inflammatory protein found in mucosal secretions. Western blot analysis revealed that bioactive CVL contained more immunoreactive MRP-8 than samples without bioactivity. The HIV-inducing activity of MRP-8 was further confirmed by showing that human recombinant MRP-8 increased HIV expression by up to 40-fold.ConclusionsMRP-8 in cervico-vaginal secretions stimulates HIV production. Strategies aimed at blocking MRP-8 activity in the genital tract could reduce risk of sexual as well as maternal–infant transmission of HIV.