Fresh and organ-culture preserved human corneas were examined for HLA-A,B,C (class I) and HLA-DR (class II) histocompatibility antigens using mouse monoclonal antibodies and an indirect immunofluorescence technique. HLA-A,B,C antigens were detected on epithelial cells and on keratocytes, but not on endothelial cells in fresh corneas. The expression of HLA-A,B,C antigens was not significantly altered by organ-culture for a period up to 7 days. The epithelial cell layer bearing the larger part of the HLA-A,B,C antigens decreased, however, from 6-7 layers to 2-3 during organ culture. HLA-DR antigens were not detected on any of the corneal layers, but were present on scattered dendritic cells within the corneal epithelium and on cells in the corneal stroma just beneath the Bowman's membrane. Using immunofluorescence, no cells bearing HLA-DR antigens were seen in cornea sections obtained after 1 week in organ-culture. These results demonstrate that the presence of HLA antigens, particularly of the HLA-DR antigens, is affected by the organ-culture preservation of the human cornea.