Leukotrienes have been shown to play a role in the pathogenesis of ocular inflammatory and allergic reactions like vernal keratoconjunctivitis and contact lens-associated giant papillary conjunctivitis. This study was designed to determine leukotriene B4 (LTB4) and leukotriene C4 (LTC4) levels in the tears of patients with ocular prosthesis-associated giant papillary conjunctivitis (OP-GPC) and to evaluate the effects of lodoxamide 0.1% on tear LTB4 and LTC4 levels of OP-GPC patients. Tear LTB4 and LTC4 levels were determined by an ELISA technique in the tears of ten OP-GPC patients before and after treatment with lodoxamide 0.1% for one month. The results were compared with that of ten healthy control subjects. The mean tear LTB4 and LTC4 levels of the OP-GPC patients were significantly higher than those of the control group. After treatment with lodoxamide 0.1%, tear LTB4 and LTC4 levels of the OP-GPC patients decreased significantly. This is the first report of elevated LTB4 and LTC4 levels in tears of OP-GPC patients and it points to the possible role of leukotrienes in the immunopathogenesis of OP-GPC. The results also indicate that lodoxamide 0.1%, a mast cell membrane stabilizer, is effective in significantly reducing tear LTB4 and LTC4 levels in OP-GPC patients.