Following determination of baseline nasal airway resistance (NAR) in human subjects, phosphate-buffered saline (PBS) was aerosolized into each nostril and NAR measurements repeated 8 times in 15 minutes. The mean maximal NAR increase in 102 subjects was 22.5% (SD +/- 24.5%) with no significant difference between atopic and nonatopic persons. Hay fever patients did not show significantly increased responsiveness to PBS while symptomatic. During 242 repeat challenges with PBS in 67 asymptomatic subjects, NAR increased over 50% in 24 tests. Following a series of 6 PBS challenges at 15-minute intervals, 10 of 71 subjects had more than a 100% increase in NAR over initial baseline values. Administration of PBS on cotton pledgets, pipetting PBS into the nose, or even just inserting a nasal speculum produced greater increases in NAR than the usual aerosol method. Intranasal atropine effectively blocked PBS-induced increases in NAR, suggesting parasympathetic stimulation as a mechanism. Isoproterenol increased NAR over 100% in 27 of 53 subjects, with no significant difference among rhinitic, asthmatic, and nonatopic individuals. This effect was inhibited by propranolol. Isoproterenol administration to 12 ragweed-sensitive subjects 15 minutes prior to ragweed challenge produced a variable inhibition in NAR responses or no protection at all. Thus the direct effects of isoproterenol on the nasal vasculature tend to outweigh those expected from inhibition of mediator release under the conditions of this study.