Murine epidermal Langerhans cells (LC) mature into potent immunostimulatory dendritic cells (DC) in vitro. This study shows that LC, when cultured for 2–3 days, resemble spleen DC in morphology and function. Initially, fresh LC are weak stimulators of T cell proliferation, but their stimulatory capacity increases significantly during culture. The LC are nonadherent, low-density cells that express Ia antigens and can be enriched to 10–50% purity. After 2–3 days in culture, LC become 3–10 times more potent than spleen DC in stimulating T cell responses. LC express Ia antigens and other markers similar to DC, and their ultrastructure and phenotype become remarkably similar to lymphoid DC. The maturation of LC in culture is not due to increased Ia levels, as the starting amount of Ia is already higher than in spleen DC. LC also develop the ability to form clusters with T cells, which may contribute to their immunostimulatory function. The study suggests that LC are precursors or immature elements of the DC system. LC are nonproliferating and nonadherent, but they can be enriched and cultured to become active stimulators of T cell responses. The results indicate that LC are immunologically immature but acquire many features of DC during culture. The study also shows that LC are distinct from macrophages and other cells, and that their function is not affected by irradiation. The findings suggest that LC may originate from bone marrow precursors and that they play a role in the induction of T-dependent immune responses. The study provides evidence that LC can mature into DC in vitro, and that they are important in the immune system.Murine epidermal Langerhans cells (LC) mature into potent immunostimulatory dendritic cells (DC) in vitro. This study shows that LC, when cultured for 2–3 days, resemble spleen DC in morphology and function. Initially, fresh LC are weak stimulators of T cell proliferation, but their stimulatory capacity increases significantly during culture. The LC are nonadherent, low-density cells that express Ia antigens and can be enriched to 10–50% purity. After 2–3 days in culture, LC become 3–10 times more potent than spleen DC in stimulating T cell responses. LC express Ia antigens and other markers similar to DC, and their ultrastructure and phenotype become remarkably similar to lymphoid DC. The maturation of LC in culture is not due to increased Ia levels, as the starting amount of Ia is already higher than in spleen DC. LC also develop the ability to form clusters with T cells, which may contribute to their immunostimulatory function. The study suggests that LC are precursors or immature elements of the DC system. LC are nonproliferating and nonadherent, but they can be enriched and cultured to become active stimulators of T cell responses. The results indicate that LC are immunologically immature but acquire many features of DC during culture. The study also shows that LC are distinct from macrophages and other cells, and that their function is not affected by irradiation. The findings suggest that LC may originate from bone marrow precursors and that they play a role in the induction of T-dependent immune responses. The study provides evidence that LC can mature into DC in vitro, and that they are important in the immune system.