During dynamic exercise, alveolar ventilation increases in proportion to oxygen uptake and carbon dioxide production. The matching of metabolic demand and ventilation is accomplished with remarkable precision, emphasizing the highly ordered structure and function of the lung parenchyma, airways, respiratory muscles and pulmonary control systems. Inspiratory and expiratory flows are reliant on airway calibre and a coordinated contraction of the respiratory musculature. The ventilatory response to exercise is thought to be governed by the principle of “minimal effort” whereby the ventilatory patterns naturally adopted are the least costly in terms of energy expenditure. However, much of what is known about the mechanics and energetics of breathing with exercise is based upon studies utilizing young male participants. There is a growing body of evidence supporting sex-based differences in airway anatomy, which may have consequences with respect to the mechanics of breathing. The first suggestion that airways may be different between healthy men and women came in the 1980’s. It was proposed that airway size is not necessarily related to lung size and the term ‘dysanapsis’ was used to describe unequal growth and physiological variation in the geometry of the tracheobronchial tree and lung parenchyma. The concept was further expanded by using a functional assessment of airway size to show that healthy adult men have airways that are approximately 17% larger in diameter than the airways of women. These are important observations if we consider the principles of airflow whereby flow through the airway tree depends on the driving pressure and airway resistance, which is largely dictated by the radius of the airways. As such, we would predict that a woman with the same sized lungs as a man would have narrower airways and therefore higher airway resistance and greater tendency towards turbulent airflow. While smaller airways may not affect individuals at low ventilations, it may be of consequence under physiological conditions where of high ventilatory demand, such as dynamic exercise. Our overall working hypothesis, and the focus of this presentation, is that anatomically based sex-differences in airway size become critical to the integrated pulmonary response to dynamic whole-body exercise. This presentation will discuss the emerging evidence for sex-based differences in human airways and the associated effects. Emphasis will be placed on observations demonstrating that endurance-trained women are more likely to exhibit mechanical ventilatory constraint and a greater work of breathing during exercise than endurance-trained men. We will highlight our recent findings that relative to men, women have a greater absolute oxygen cost of breathing for a given level of ventilation, and this represents a greater fraction of total oxygen uptake. We will also stress what we view as questions that would benefit from additional research.