We recorded wheezes, pleural pressure, plethysmographic lung volumes and mouth flow rates in 6 healthy subjects during maximal expiratory maneuvers breathing air and a mixture of 80% He-20% O2 (He) before and after methacholine inhalation. During expiratory flow maneuvers a critical pleural pressure was needed before wheezes occurred. All but one wheeze occurred in the last two thirds of vital capacity during forced exhalation where flow limitation existed. At a flow rate of 2 liters/s, the critical pleural pressure breathing air was 21 +/- 5.8 cm H2O (mean +/- SD), whereas that of breathing He was higher: 32 +/- 7.8 cm H2O (p less than 0.02). In addition the wheezes occurred at lower lung volumes (associated with small airway diameters) when He was breathed instead of air. This was seen both before (p less than 0.02) and after (p less than 0.01) methacholine. These findings suggested that for a given flow rate a lighter gas such as He had to acquire a higher linear velocity so that the convective acceleration was sufficient to produce wheezes. This was achieved by either an increase in the driving critical pleural pressure or narrowing of bronchi by a larger compressing pleural pressure or smaller lung volumes.