We have developed an in vitro reconstructed vaginal mucosa integrating Langerhans cells (LCs), obtained by differentiation of umbilical cord blood CD34⁺ hematopoietic progenitor cells, and, in this model, we have investigated the infection of LCs by human immunodeficiency virus type 1 (HIV-1). Proviral DNA of X4 (LAI and NL4-3) and R5 (Ba-L) HIV-1 strains were detected in LCs integrated in the reconstituted mucosa. Infection of LCs could be specifically inhibited by the chemokines stromal cell-derived factor 1 (SDF-1) and RANTES (regulated on activation, normally T cell-expressed and -secreted), confirming the presence of functional coreceptors on LCs generated in vitro. A complete inhibition of LCs, by use of a zidothymidine, a reverse transcriptase inhibitor, was also observed. Moreover, HIV-1-infected LCs of the reconstructed mucosa wereable to transmit R5 or X4 HIV-1 strains to activated peripheral blood mononuclear cells. Such a model couldbe a useful tool to study the mechanisms involved in transmission of HIV in the female genital tract.