Histamine-induced nasal hyperpermeability was measured in rats. Perfusion of histamine elicited a biphasic increase of nasal vascular permeability, and an increase of concentration of platelet-activating factor (PAF) in the perfusate. Both phases were prevented by pretreatment with diphenhydramine (1 mg/kg, p.o.), a histamine H1-receptor antagonist, and the second increase of vascular permeability was prevented by pretreatment with 3-[4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f] [1,2,4]-triazolo [4,3-alpha] [1,4] diazepin-2-yl]-1-(4-morpholinyl)-1-propane (WEB 2086) (10 mg/kg, p.o.), an anti PAF agent. The time-course of PAF-induced nasal hyperpermeability was similar to that of the second increase induced by histamine. These findings suggest that PAF released by histamine from nasal mucosa plays an important role in nasal allergy, especially in the late phase.