In the present study, hypertrophic and metaplastic changes of goblet cells were induced in rat nasal epithelium by intranasal instillation of endotoxin or elastase. A significant increase in the amount of intraepithelial mucosubstance was observed after 24 hours during 3 days of instillation. The elastase-induced mucus production was not inhibited in neutrophil-depleted rats, but the endotoxin-induced change was significantly inhibited. Intranasal instillation of the neutrophil elastase inhibitor ONO-5046 partially inhibited the endotoxin-induced mucus production. Epithelial mucus secretion was evaluated by the temporary decrease in the amount of intraepithelial mucosubstance. The endotoxin-induced mucus secretion peaked 3 to 6 hours after intranasal instillation, coinciding with the peak of the intraepithelial neutrophil infiltration. The elastase-induced mucus secretion peaked 1 to 3 hours after intranasal instillation; intraepithelial neutrophil infiltration was not induced by elastase. These results indicate that neutrophil elastase is an important mediator of the intraepithelial mucus synthesis and secretion induced by endotoxin.