Earlier work has identified a cell population that replicates HIV-1 in the absence of standard T cell stimuli. The system consists of dendritic cells and memory T lymphocytes that emigrate from organ cultures of human skin and together support a productive infection with HIV-1. These emigrants resemble cells that can be found in mucous membranes and that normally traffic in afferent lymph. Here, we report that a low level of infection in the dendritic cell can initiate extensive HIV-1 replication in cocultures with T cells. First we extended our earlier work to larger skin specimens from cadavers. As long as the organ cultures were set up within 36 h of death, the emigrant leukocytes were comparable to cells from fresh surgical specimens in number, phenotype, and function. These mixtures of dendritic cells and T cells provided the milieu for a productive infection with several virus isolates. When purified dendritic cells were separately pulsed with virus and then mixed with T cells that had not been pulsed with HIV-1, active infection ensued. The infectivity of HIV-pulsed dendritic cells persisted for at least 1.5 d in culture, but was blocked if AZT was added during that time to block reverse transcription in the dendritic cells. The number of copies of proviral DNA in the dendritic cells corresponded to < 100 copies per 5 X 10(4) cells, but upon mixing with T cells, > 10(4) copies were found 5-7 d later. By contacting syngeneic T cells, extralymphoid depots of dendritic cells--even with a low viral burden as has been reported in vivo--may contribute to chronic HIV-1 replication in infected individuals.