The roles of sialyl-Lewisx antigen were evaluated in the pathogenesis of psoriasis. Sialyl-Lewisx expression was investigated immunohistochemically in the epidermis of normal human skin and erythematous lesional skin of psoriasis vulgaris by avidin-biotin-peroxidase complex procedures. A few sialyl-Lewisx positive dendritic cells were detected in the epidermis of normal human skin. In 7 out of 9 cases of psoriasis vulgaris, the number of sialyl-Lewisx-positive epidermal dendritic cells increased in the erythematous lesion over the adjacent normal skin; there were no marked changes in the numbers of CD1a-positive cells in the epidermis between the two skin types. In the double immunofluorescence studies, more than half of the sialyl-Lewisx-positive epidermal cells in psoriatic erythema were stained with a monoclonal Lag antibody that specifically reacts with Birbeck granules and related structures of human Langerhans cells. Furthermore, we determined the changes in serum levels of sialyl-Lewisx antigens in patients with psoriasis. Although levels in the sera were not significantly elevated over those of controls, the increases correlated with the degree of disease activity. These findings suggest that sialyl-Lewisx antigen is possibly involved in the development of psoriasis.