CD68 is a myelomonocytic marker identified in human dermal macrophages. Although the existence of CD68 + dendritic epidermal cells has been reported, their characteristics have not been well elucidated. Cutaneous lymphocyte-associated antigen (CLA) is a homing receptor of cutaneous inflammatory T cells. Our recent report suggested that CLA was a homing molecule of CD1a+ Langerhans cells (LC) in the skin. In the present study we tested whether CD68 and CLA+ dendritic epidermal cells were present in skin specimens of normal skin and diseased skin such as lichen planus (LP), psoriasis vulgaris (PS), discoid lupus erythematosus (DLE), basal cell epithelioma (BCE), squamous cell carcinoma (SCC), irritated seborrheic keratosis (iSK), and Bowen's disease (BD). CD68+ dendritic epidermal cells were identified in normal skin and consisted of half the population of CD1a+ LC. These data indicate that CD68+ dendritic epidermal cells constitute a subpopulation of CD1a+ LC. CLA was expressed on a small percentage of CD68+ dendritic epidermal cells in normal skin. A remarkably increased number of CD68+ dendritic epidermal cells and upregulation of CLA on CD68+ dendritic epidermal cells were observed in diseased skin. The percentage of CLA+ cells among all CD68+ dendritic epidermal cells was less than that of CLA+ cells among all CD1a+ LC in diseased skin. The percentage of CLA+ cells among all CD68+ dendritic dermal cells was much less than that of CLA+ cells among all CD1a+ dendritic dermal cells. In normal skin, the epidermis showed minimal expression of monocyte chemoattractant protein (MCP)-1 and TGF-beta2, and no expression of TGF-beta1. In diseased skin, the epidermis showed elevated, but still moderate immunoreactivity for MCP-1. Slightly enhanced immunoreactivity for TGF-beta2, but not for TGF-beta1, was observed in the epidermis of diseased skin. Increased epidermal MCP-1 immunohistochemical staining was associated with the increased number of CD68 dendritic epidermal cells. These data suggest the possibility that MCP-1 secretion from the epidermis can affect the migration of CD68; Cutaneous lymphocyte-associated antigen; Monocyte chemoattractant protein-1; TAF-beta.