Contact lens-associated giant papillary conjunctivitis (CL-GPC) caused by mechanical and immune mechanisms is a significant problem resulting in contact lens intolerance and discontinuation of contact lens wear. In the present study, tear fluid leukotriene C4 (LTC4) level was evaluated in soft contact lens wearers with and without CL-GPC using ELISA. Statistical analysis showed no significant difference in tear fluid LTC4 between contact lens wearers without GPC and normal controls (p>0.05), but a significant increase in tear LTC4 level in CL-GPC patients (p<0.05). On the basis of this finding, it might be possible to explain redness, conjunctival edema, increased mucoid secretion, and papillary changes by the effect of LTC4 on eye tissues. Effective treatment of CL-GPC might be possible in the future by employing inhibitors of leukotriene synthesis and action.