The purpose of this study was to investigate the involvement of chemical mediators other than histamine in nasal allergic signs using histamine H(1) receptor-deficient mice. In passively sensitized mice, antigen instillation into the nasal cavity induced significant increases in sneezing and nasal rubbing in wild-type mice, but no such increases were observed in histamine H(1) receptor-deficient mice. In actively sensitized mice, both sneezing and nasal rubbing were also significantly increased in a dose-dependent manner in both wild-type and histamine H(1) receptor-deficient mice. Histamine H(1) receptor antagonists such as cetirizine and epinastine significantly inhibited antigen-induced nasal allergic signs in wild-type mice, although the effects were incomplete. In addition, the thromboxane A(2) receptor antagonist ramatroban also inhibited these responses in wild-type mice. However, the leukotriene receptor antagonist zafirlukast showed no effects in wild-type mice. These results suggested that in the acute allergic model (passive sensitization), only histamine H(1) receptors are related to nasal signs induced by antigen, whereas in the chronic allergic model (active sensitization), both histamine H(1) receptors and thromboxane A(2) receptors were involved in the responses.