We compared the functional capacities of human epidermal Langerhans cells (LC) and peripheral blood monocytes. Epidermal sheets were obtained by a suction blister device. After enzymatic treatment LC were enriched by attaching them to IgG-located erythrocyte monolayers. On a per cell basis, LC were several times more efficient accessory cells than monocytes in augmenting nickel-and tuberculin (PPD)-induced T-cell proliferation. In mixed cell cultures LC stimulated both autologous and allogeneic T cells, whereas monocytes stimulated only allogeneic cells. In addition, LC were significantly more potent allogeneic stimulators than monocytes. Although monocytes were weaker accessory cells and allogeneic stimulators than LC, they induced higher interleukin 1 (IL-1) activities than LC-enriched or LC-depleted cells. These results indicate that there are functional differences between LC and monocytes and that antigen presentation and mediator secretion are not correlated.