PURPOSE: The primary ocular targets of chronic graft-versus-host disease (GVHD) are the lacrimal gland (LG) and the conjunctiva, and their involvement results in keratoconjunctivitis sicca (KCS). The purpose of the present study was to evaluate the frequency of signs and symptoms of KCS present in patients submitted to BMT, to identify the cellular phenotype of the conjunctival and lacrimal gland biopsies of these patients by immunohistochemistry and to correlate the findings with the presence of dry eye due to GVHD. METHODS: Forty-seven patients were clinically classified into two groups: Group I, with ocular GVHD, submitted to allogeneic BMT and Group II, without ocular GVHD, submitted to autologous and allogeneic BMT. Thorough eye examination, including clinical lacrimal function tests and biopsies of the conjunctiva and of the LG were performed in the pre- and posttransplantation period. The biopsies were submitted to immunohistochemical analysis using a panel of monoclonal antibodies. RESULTS: Of the 28 (82.4%) patients with chronic GVHD, 13 (46.4%) presented ocular GVHD. Of the six patients without GVHD, one (16.7%) presented ocular GVHD. None of those submitted to autologous BMT presented ocular GVHD and 14 (41.2%) of 34 patients with allogeneic BMT presented ocular GVHD. All patients with ocular GVHD (Group I) had symptoms and the most frequent were burning, foreign body sensation, blurred vision and dryness. The rose bengal test was one of the most sensitive in this study and slit lamp examination was very useful in the evaluation of corneal and conjunctival alterations, since these alterations were always present in patients with dry eye in our study. Neither symptoms and signs of dry eye nor significant immunologic reaction was observed in the conjunctiva and in the LG of patients without ocular GVHD (Group II). There was an increase in the T lymphocyte population, of T helper lymphocyte (Th/i) and T suppressor-cytotoxic lymphocyte (Ts/c) subpopulation in the conjunctiva and in the LG of patients with ocular GVHD after the transplantation. CONCLUSIONS: Patients submitted to allogeneic BMT may develop ocular GHVD characterized by KCS. The immunohistochemical study of the conjunctiva and lacrimal gland biopsies of these patients suggested that these tissues are the target of the T cell mediated immunological reaction.