Langerhans cells (LC) in normal human corneas (with the exception of newborns) lack thymocyte antigen T6, a highly specific marker for noncorneal LC. Because corneal LC could not be induced to express T6 antigen when cultured with various cytokines including interleukin-1 (shown to modulate T6 expression on gingival LC), some authors assume that corneal LC may represent a distinct LC subpopulation that is innately inactive. In this study, 62 corneas from patients with various corneal diseases were investigated for the presence of T6 and histocompatibility antigen HLA-DR on LC in the central and pericentral epithelium. Both T6- and HLA-DR-positive LC at a high density similar to that observed in normal epidermis could be detected in the epithelium of five corneas with epidermalization after alkali burns. Furthermore T6- and HLA-DR-positive LC at smaller densities also were detected in corneas from patients with chronic herpetic stromal keratitis, zoster keratitis, chronic allograft rejection, and bacterial corneal ulcers. Although the functional significance of T6 expression on corneal LC remains to be determined, the induction of T6 antigen on corneal LC may represent an important event for the antigen-presenting function of these cells in various corneal diseases including corneal allograft rejection.