Flow limitation during a maximum expiratory flow-volume curve (MEFVC) while breathing air occurs at lung volumes below 70% vital capacity (VC). To evaluate small airways function, use has been made of the volume of isoflow (VisoV), comparing an MEFVC done in air to one done in 80% helium, 20% O2 (HeO2). The VisoV has high intra-subject variability. This study investigated whether this variability was due to an inability to flow limit while breathing HeO2. This would occur if the velocity of expiratory muscle contraction did not result in sufficient intrathoracic pressures to cause dynamic airway compression in the face of increased expiratory flows while breathing HeO2. Seven healthy adult male subjects performed repeated VC expirations of varying effort with an esophageal balloon in place in a body plethysmograph while breathing air and HeO2. The flow-volume curves were matched at residual volume and transpulmonary pressure-flow plots were constructed at volume isopleths of 70, 50, and 25% VC. In air, flow limitation was demonstrated in 3, 6, and 7 subjects at 70, 50, and 25% VC, respectively. In HeO2, flow limitation was achieved in 1 and 4 subjects at 70 and 50% VC. Although one subject demonstrated intermittent glottic closure, the remaining 6 demonstrated flow limitation at 25% VC. We concluded that dynamic airways compression occurs even with the increased flows in HeO2.