To examine the roles of alpha-adrenergic, beta-adrenergic and cholinergic agonists on the nasal secretion mechanism, the author repeated nasal methacholine (Mch, 1 time 20 mg) challenges ten times at 10-min intervals in 13 healthy male subjects. As it was difficult to obtain a sufficient amount of nasal secretion for analysis using simple nasal provocation tests with alpha-and beta-adrenergic agonists before repeated Mch challenges, alpha-adrenergic (phenylephrine, Phe, 2 mg) and beta-adrenergic (isoproterenol, Iso, 0.2 mg) agonists were administered into both nostrils. The effects of these agents on the volume of nasal secretions (Vol), the fucose volume (Fu, an index of glandular secretion) and the albumin volume (Alb, an index of vascular permeability) in the Mch induced nasal secretions were analyzed each time. Repeated Mch challenges revealed that the initial challenge produced the largest response as reflected by the Vol, Fu and Alb of the secretions, and by Vol and Fu production being almost constant during the 10 repetitions of Mch challenge at 10-min intervals. However, Alb demonstrated the greatest decrements. Phe administration before Mch challenges gave rise to Fu increasing more markedly while Alb was unchanged. On the other hand, that of Iso before, produced greater decreases in Vol, Fu and Alb levels. Therefore, it is suggested that repeated Mch challenge causes the maintenance of glandular secretion while stopping albumin permeability, that with pre-administration of alpha-agonists glandular secretion increases, and that pre-administration of beta-agonists inhibits glandular secretion. When both alpha- and beta-agonists are given before the challenge, however, there is no increase in vascular permeability.