The mechanism by which airway cooling induces airflow obstruction in asthmatic subjects has not yet been established. Using a pair of isocapnic hyperventilation challenges, with a 40-minute interval, we looked for the presence of a refractory period in 19 asthmatic patients (aged 9-18 years). The subjects fell into two groups. The eight in the "non-refractory" group showed less than a 25% reduction in response to the second challenge, but the 11 in the "refractory" group showed at least a 35% reduction. Twelve subjects also performed a hyperventilation challenge after cholinergic blockade with inhaled ipratropium bromide. In five, in whom no refractoriness after hyperventilation was seen, there was a significant protection from cholinergic blockade (p less than 0.05). In these a vagal (cholinergic) reflex seems likely. The remaining seven, who had a refractory period, received no significant protection from cholinergic blockade and therefore no evidence for the presence of any cholinergic mechanism. We conclude that two mechanisms are responsible for hyperventilation-induced asthma, one of which is a vagal reflex while mediator release may be the other.