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A report that genetic subtype E human immunodeficiency virus type 1 (HIV-1) strains display a preferential tropism for Langerhans cells (epidermal dendritic cells [DCs]) compared to genetic subtype B strains suggested a possible explanation for the rapid heterosexual spread of subtype E strains in Thailand (L. E. Soto-Ramirez et al., Science 271:1291-1293, 1996). In an independent system, we applied subtype E and B isolates to skin leukocytes, since skin is a relevant model for the histologically comparable surfaces of the vagina and ectocervix. Isolates of both HIV-1 subtypes infected DC-T-cell mixtures, and no subtype-specific pattern of infection was observed. Purified DCs did not support the replication of strains of either subtype B or E. Our findings do not support the conclusion that subtype E strains have a preferential tropism for DCs, suggesting that other explanations for the rapid heterosexual spread of subtype E strains in Asia should be considered.