The mucosal surface of the eye interfaces with the environment and can detect the presence of pathogens and irritants. The mucosal cells respond by up-regulating genes whose products either directly attack the contaminant or recruit leukocytes through the release of cytokines. Mucin, an epithelial glycoprotein, traps contaminants and aids in their removal through normal tear clearance mechanisms. Using Northern analysis and reverse transcription-polymerase chain reaction, we have found that MUC1, a membrane-bound ocular surface mucin, is up-regulated following exposure to the products of both bacteria and activated lymphocytes. Consistent with this, MUC1 gene expression is also up-regulated in corneal epithelial cells exposed to precorneal tear film collected from two rigid contact lens wearers. The changes in MUC1 gene expression during exposure to potential ocular irritants suggest that analysis of the molecular mechanisms mediating these changes may reveal control points amenable to drug therapy.