Respiratory function was evaluated in 12 healthy and 13 asthmatic volunteers following a single oral dose of pyridostigmine in a double-blind, placebo-controlled cross-over study. Respiratory function tests were performed at rest and after submaximal exercise at the time corresponding to the expected peak cholinesterase inhibition by pyridostigmine. A single dose of 60 mg pyridostigmine given to nonasthmatic subjects led to a decrease of 28.4% in cholinesterase activity when compared to the baseline and a statistically (but not physiologically) significant decrease in FEV1 (forced expiratory volume in 1 sec) both at rest (P less than 0.015) and after exercise (P less than 0.05). This effect showed a strong correlation to the degree of cholinesterase inhibition (r = -0.936, P less than 0.0001). According to these findings, a smaller dose of pyridostigmine (30 mg) was given to subjects with mild bronchial asthma. At that dose, pyridostigmine resulted in a similar inhibition of cholinesterase activity to a mean of 76.7% of the baseline. A significant decrease in the pulse rate was also found (P less than 0.005). However, no changes in respiratory function were observed when compared with the effects of placebo. The effect of post-exertion atropine inhalation on respiratory function was also unchanged with pyridostigmine at that dose. We conclude that, in general, at this dose pyridostigmine is a safe drug for asthmatics; however, the distribution of individual results in this group cannot preclude the existence of a subpopulation of asthmatic patients who are more vulnerable to the effects of pyridostigmine.