The expression of HLA-DR antigen on keratinocytes has recently been described as a frequent finding in various dermatologic disorders without restriction to a particular entity or a peculiar histologic reaction pattern, except for the association with a mononuclear dermal infiltrate. To determine the relationship of HLA-DR + keratinocytes and T lymphocyte epidermotropism in human disease in vivo, 82 skin specimens were investigated by immunohistologic and stereologic methods and by two- and three-dimensional linear regression analysis. In randomly selected cases of various dermatoses, HLA-DR+ keratinocytes were associated with T lymphocyte epidermotropism. Furthermore, HLA-DR + keratinocytes correlated particularly with the proportion of epidermotropic suppressor/cytotoxic cells. Our findings demonstrate that HLA-DR + keratinocytes are associated with a particular pattern of epidermotropism, which may suggest an interaction of keratinocytes and T suppressor/cytotoxic cells in vivo.