The effects of two new immunosuppressors, FK-506 and mizoribine, on antigen-induced bronchial inflammation and reactivity to acetylcholine in mice were studied in comparison with those of cyclosporin A and cyclophosphamide. Three inhalations of an antigen by actively sensitized BALB/c mice resulted in an increase in airway reactivity to acetylcholine. Twenty-four hours after the final inhalation, the number of leukocytes (mononuclear cells and eosinophils) and the amount of interleukin 5 (IL-5) increased significantly. In BALB/c nu/nu mice (athymic mice), three inhalations of antigen caused no significant change in either airway inflammation or hyperresponsiveness. The administration of each of the four immunosuppressors clearly inhibited antigen-induced airway eosinophilia. Moreover, FK-506, mizoribine and cyclophosphamide clearly inhibited the antigen-induced IL-5 production and cyclosporin A showed the tendency to inhibit IL-5 production. Whereas FK-506, mizoribine and cyclosporin A clearly inhibited the antigen-induced airway hyperreactivity in BALB/c mice, cyclophosphamide did not show a significant effect on this airway hyperreactivity. These results indicate that FK-506, mizoribine and cyclosporin A, but not cyclophosphamide, inhibit antigen-induced airway hyperreactivity in mice. The mechanism which inhibits antigen-induced airway eosinophilia and IL-5 production is not involved in the inhibitory mechanism of airway hyperreactivity by FK-506 and mizoribine.