An immunoelectron-microscopic technique was applied to investigate the localization of molecules that are involved in the elicitation of allergic contact dermatitis in human epidermal cells in situ. Langerhans cells in the epidermis of lesions showed a strongly increased cell surface expression of HLA class II molecules as compared with normal skin. In addition, a high number of intracellularly located HLA class II molecules were present in Langerhans cells of lesional epidermis, suggesting increased biosynthesis of these molecules during the elicitation process. In contrast, no differences in the expression of CD1a by Langerhans cells was observed between normal and lesional skin. Frequently, the Langerhans cells were found in close apposition to mononuclear cells, which also exhibited a strong cell surface HLA class II expression. The number of Birbeck granules that are characteristic intracellular Langerhans cells organelles was increased in lesional Langerhans cells as compared with normal-skin Langerhans cells, which may correlate with the activated state of lesional Langerhans cells. These Birbeck granules were always HLA class II or CD1a negative. The increased synthesis and expression of HLA class II molecules on the cell surface of Langerhans cells suggests a direct role for these HLA class II molecules in the elicitation process of allergic contact dermatitis.