Two subsets of dendritic cells, differing in T-cell stimulatory function, have been purified directly from human blood. Both subsets are positive for major histocompatibility complex (MHC) class II expression and negative for lineage-specific antigens (e.g. CD3, CD14, CD16, CD19 negative), but are separated by exploiting differences in expression of the beta 2-integrin, CD11c. The CD11c-negative subset is functionally immature, requiring monocyte-derived cytokines to develop into typical dendritic cells. The CD11c-positive subset has potent T-cell stimulating activity and expresses the activation antigen CD45RO, unlike its immature counterpart. However, these mature cells only develop typical dendritic morphology and high levels of MHC proteins and adhesins after a period of culture independent of exogenous cytokines. Although the freshly isolated mature dendritic cells resemble monocytes in cytospin preparations, the former lack CD14 and have a much stronger primary T-cell stimulatory capacity. We hypothesize that the CD11c-negative immature cells are marrow-derived precursors to tissue dendritic cells, such as epidermal Langerhans' cells, while the CD11c-positive cells are derived from tissues where they have been activated by antigen, and are en route to the spleen or lymph nodes to stimulate T-cell responses there.