To estimate the involvement of thromboxane (Tx) A2 in the onset of nasal blockage, we examined the effect of the selective TxA2 receptor antagonist, S-1452, as well as an H1-antihistamine, diphenhydramine, on the antigen-induced increase in intranasal pressure, as an index of nasal blockage, in anesthetized guinea pigs actively sensitized by inhalation of aerosolized ovalbumin (OA). Oral administration of S-1452 or intravenous administration of diphenhydramine significantly but incompletely reduced the increase in intranasal pressure following exposure of the nasal cavity of guinea pigs to aerosolized OA. In combination, the two agents were more effective than either alone, but there was no significant difference between them. The TxB2 level was significantly elevated in nasal lavage fluid 15 and 30 min after antigen challenge. Exposure of the nasal cavity of guinea pigs to aerosolized U-46619, a TxA2 mimetic, also resulted in a marked increase in intranasal pressure, and this could be almost completely suppressed by S-1452. These findings suggest that TxA2 contributes to antigen-induced nasal blockage in guinea pigs.