To determine the influence of bronchoconstriction on the distribution of ventilation during an asthma attack, pulmonary clearance of 133xenon was evaluated in four normal and eight asthmatic subjects within three to five minutes after intramuscular injection of methacholine. In asthmatics, administration of 4-10 mg methacholine resulted in a decrease of forced vital capacity of 28.5 +/- 5.1 (SE) percent and a decrease in expiratory flow at 60 percent vital capacity of 44.2 +/- 6.9 percent (P less than 0.001). The cumulative ventilation required to reach 50 percent of the pre-washout radioactivity increased from 3.6 +/- 0.8 to 9.9 +/- 1.6 L after administration of the drug (P less than 0.05). The normal subjects showed no ventilatory effects after receiving 10 mg methacholine. Comparison of clearance of 133xenon from ten areas of lung (each representing approximately 6 percent of the surface area of one lung) showed that all areas were affected to approximately the same extent during drug-induced asthma. These findings suggest that parenteral methacholine is an effective way to demonstrate airway hyperreactivity and that the airway response to methacholine in asthmatics is relatively generalized throughout the lung.