To dissect the early events in the transmission of HIV-1 from mother to child, we investigated whether DCs participate in HIV-1 entry into human small intestinal mucosa. We isolated human MNLs from jejunal lamina propria and identified a subpopulation of CD11c+HLA-DR+ MNLs that expressed DC-SIGN, CD83, CD86, CD206, and CCR7, indicating a DC phenotype. Jejunal DCs also expressed the HIV-1 receptor CD4 and coreceptors CCR5 and CXCR4 and in suspension rapidly took up cell-free HIV-1. HIV-1 inoculated onto the apical surface of explanted jejunum was transported by lamina propria DCs through the mucosa and transmitted in trans to blood and intestinal lymphocytes. These findings indicate that in addition to intestinal epithelial cells, which we showed previously transcytose infectious HIV-1 to indicator cells, intestinal DCs play an important role in transporting HIV-1 through the intestinal mucosa and the subsequent transmission to T cells. © Society for Leukocyte Biology.