Purpose: To identify functional subsets of inflammatory cells and expression of cytokines in the conjunctiva of patients with ocular prosthesis-associated giant papillary conjunctivitis (P-GPC). Methods: Specific immunohistochemical staining using monoclonal antibodies was performed on biopsy specimens obtained from superior tarsal conjunctiva of 18 patients with P-GPC. The prosthetic eyes were taken as the study group, whereas their fellow eyes were used as matched controls. Results: In normal conjunctiva, mast cells (MCs) were locatedonly in the substantia propria (SP), whereas in P-GPC eyes MCs were also notable in the epithelium in five specimens. Tryptase-chymase-positive MCs (MCTC) were predominant both in P-GPC (79%) and in fellow (72%) eyes. MCTC, CD4 + lymphocyte, CD8 + lymphocyte and eosinophil numbers were higher in P-GPC specimens compared with the fellow eyes (P = 0.005, 0.074, 0.012 and 0.025, respectively). Eosinophils were detected in 58.8% of P-GPC specimens and 16.7% of control specimens (P = 0.053). The number of inflammatory cells expressing eotaxin and interleukin (IL)-4 was higher in P-GPC group (P = 0.050 and 0.048, respectively). Nine out of 17 giant papillary conjunctivitis specimens (52.9%) showed eotaxin and IL-4 immunoreactivity, which was considerably higher than the fellow eyes (16.7%) (P = 0.064). Conclusion: These findings suggest that P-GPC is an allergic disease of the eye associated with increased numbers of MC, eosinophils and lymphocytes in the conjunctiva and a remarkable expression of IL-4 and eotaxin both by the conjunctival epithelium and by the inflammatory cells in the SP. © 2007 The Authors; Journal compilation © 2007 Royal Australian and New Zealand College of Ophthalmologists.