A study of histopathologic changes, ultrastructure, and expression of the HLA-Dr antigen within the giant papillae of patients with giant papillary conjunctivitis was performed to determine whether cell-mediated immune response is related to this condition. Conjunctival giant papillae from ten patients with giant papillary conjunctivitis were examined by light and electron microscopy and by the indirect immunofluorescent staining method with HLA-Dr antibody. The infiltration of eosinophilic neutrophils and granules was most prominent, with the occasional infiltration of mast cells, as shown by light microscopy. The infiltration of activated fibroblasts and Langerhans cells was also observed. Cells expressing HLA-Dr antigen were also markedly increased, as shown by the immunofluorescent method. These findings suggest that delayed hypersensitivity may, along with the processes of antigen presentation by HLA-Dr-expressing (including Langerhans) cells, contribute to the pathogenesis of giant papillary conjunctivitis.