We examined the effect of pyridostigmine (PY) at a dose of 30 mg orally three times a day on nonspecific bronchial hyperreactivity in ten normal nonsmokers (NNS), ten smokers (SM), and ten mild asthmatics (AS). We conducted a double-blind, placebo-controlled, crossover trial, randomly assigning subjects to receive either placebo (PL) or PY before undergoing bronchoprovocation challenge with eucapnic voluntary hyperventilation (EVH) using dry gas. Compliance with PY was confirmed by measuring red blood cell acetylcholinesterase (Achase) levels during both days of testing. While taking PL, the mean (+/- SEM) falls in FVC and FEV, after the bronchoprovocation were as follows: NNS, 1.0 percent (+/- 0.6) FVC and 4.3 percent +/- 1.0) FEV1; SM, 2.4 percent (+/- 1.1) FVC and 2.7 percent +/- 1.3) FEV1; AS, 5.3 percent (+/- 2.3) FVC and 11.5 percent +/- 2.8) FEV1. The mean decreases in FVC and FEV1 while taking PY were as follows: NNS, 1.8 percent (+/- 0.7) FVC and 4.3 percent (+/- 0.8) FEV1; SM, 3.8 percent (+/- 1.4) FVC and 5.2 percent (+/- 1.6) FEV1; AS, 4.4 percent (+/- 1.3) FVC and 11.8 percent (+/- 2.8) FEV1. Within each category, using a paired t test to compare the results on each day of testing, no statistically significant differences were noted. Pyridostigmine at the tested dose has no significant effect on nonspecific bronchial hyperreactivity in normal NNS, SM, or AS.