A mixture of 80% helium and 20% oxygen has physical properties that increase airflow and decrease resistance in the airway when used as a portion of inspired gas. This study was designed to demonstrate and quantify the effects of a helium-oxygen mixture in a normal airway and when airway resistance is increased. Thirty healthy volunteers were studied breathing room air and the helium-oxygen mixture through a normal airway and an airway that included a resistor. Pulmonary function tests, directed by a registered respiratory therapist, were performed on all subjects using a computerized spirometer. The functional vital capacity, one-second forced expiratory volume, half-second forced expiratory volume, and peak inspiratory flow rate were analyzed. There was a statistically significant increase in 1-second forced expiratory volume using a helium-oxygen mixture in a normal airway. All pulmonary function test scores statistically improved when volunteers inspired helium and oxygen through the restricted airway, demonstrating that helium and oxygen can increase airflow in the presence of an increased airway resistance. This substantiates a role for helium and oxygen in treating conditions associated with decreased airway size and increased airway resistance.