Lactoferrin, an iron complexing protein in normal tears, is an important component of the nonspecific host defense system of the external eye. We measured tear lactoferrin levels in patients with contact lens-induced giant papillary conjunctivitis (GPC) by an enzyme-linked immunosorbent assay (ELISA). Patients with active GPC (N = 26) had significantly reduced tear levels of lactoferrin (0.876 +/- 0.42 mg/ml) compared with normal individuals (N = 12; 1.73 +/- 0.46 mg/ml, P less than 0.0003) and the control contact lens wearers' group (N = 11; 1.57 +/- 0.92 mg/ml, P less than 0.003). Patients with vernal conjunctivitis (N = 10), an ocular disease with similar histopathology, had slightly reduced concentrations of tear lactoferrin (1.22 +/- 0.59 mg/ml). Patients with inactive GPC (N = 7) had normal tear levels of lactoferrin (1.33 +/- 0.49 mg/ml). The lactoferrin to total protein ratio in the tears was significantly reduced in patients with GPC compared to normal subjects, control contact lens wearers, and patients with inactive GPC. The decreased tear levels of lactoferrin in patients with GPC may contribute to increased coating of lenses with bacteria and their products and enhanced ocular inflammation which may play a role in the pathogenesis of GPC.