Background: IL-4 and IL-13 play a putative role in mucus hypersecretion in asthma. Suplatast tosilate prevents the synthesis of T H2 cytokines. Objective: Because suplatast tosilate inhibits T H2 cytokines but does not inhibits IFN-γ production, we examined the effect of suplatast on IL-4– or IL-13– and ovalbumin (OVA)-induced mucin synthesis in NCI-H292 cells in vitro and in bronchi of pathogen-free BALB/c mice in vivo. Methods: In vitro, NCI-H292 cells were preincubated with suplatast tosilate (0.1-100 μg/mL) 1 hour before adding human recombinant IL-4 (10 ng/mL). In vivo, mouse recombinant IL-4 or IL-13 (250 ng per/mouse) was instilled intranasally in mice pretreated with suplatast tosilate (50 mg·kg –1 ·d –1 ). Mucous glycoconjugates were stained with Alcian blue (AB)/periodic acid–Schiff (PAS) stain. To evaluate effects of suplatast tosilate on goblet-cell metaplasia in OVA-sensitized mice, animals were pretreated with suplatast tosilate (1-50 mg·kg –1 ·d –1 ) intragastrically. IL-4 and IL-13 were measured, and allergic inflammatory cells were analyzed in bronchoalveolar lavage fluid of OVA-sensitized mice. Results: Pretreatment with suplastast did not prevent IL-4– or IL-13–induced increase in mucous glycoconjugate production in NCI-H292 cells or in mice. OVA sensitization increased AB/PAS-stained area of the epithelium (48.1% ± 2.4%, P < .01 compared with control mice). Suplatast tosilate inhibited OVA-induced goblet-cell metaplasia in airway epithelium in a dose-dependent fashion; 50 mg·kg –1 ·d –1 decreased the AB/PAS area to 22.7% ± 2.7% (P < .05 compared with OVA sensitization alone). Pretreatment with suplatast tosilate also prevented OVA-induced increase in IL-4 and IL-13 levels and decreased the number of lymphocytes and eosinophils in bronchoalveolar lavage fluid (P < .05 compared with values of mice given OVA alone). Conclusion: These results indicate that suplatast tosilate prevents allergen-induced goblet-cell metaplasia and the recruitment of eosinophils and lymphocytes into the airways. These results suggest that this effect is due to the prevention of the production of T H2 cytokines in airways. (J Allergy Clin Immunol 2000;105:739-45.)