We have investigated the immunoperoxidase staining pattern in the epidermis and dermal infiltrates of highly inflamed portions of psoriatic lesions, selecting for biopsy early pinpoint lesions or margins of active plaque lesions. We found positive intercellular staining for HLA-DR antigens in localized areas of the epidermis in about half of the patients tested. In contrast, OKT6 antigen was found only on the dendritic cells in the epidermis and dermis in all cases. These findings support the hypothesis that an active cellular immune reaction involving the epidermis, possibly associated with the expression of HLA-DR antigens on keratinocytes, occurs in the highly inflamed areas of psoriatic lesions, particularly in early pinpoint lesions or at the edges of spreading plaque lesions.