What is the central question of this study? Does the combination of a higher neural respiratory drive and greater dynamic mechanical ventilatory constraints during exercise in healthy women versus men form the mechanistic basis of sex differences in activity-related dyspnoea? What is the main finding and its importance? Sex differences in activity-related dyspnoea in health primarily reflected the awareness of a higher neural respiratory drive needed to achieve any given ventilation during exercise in the setting of relatively greater dynamic mechanical ventilatory constraints in women. These findings may have implications for our understanding of the mechanisms of sex differences in exertional dyspnoea in variants of health (e.g. the elderly) and in patients with cardiorespiratory disease. The purpose of this study was to elucidate the physiological mechanisms of sex differences in exertional dyspnoea. We compared detailed measures of neural respiratory motor drive [diaphragmatic EMG (EMGdi) expressed as a percentage of maximal EMGdi (EMGdi%max)], breathing pattern, operating lung volumes, dynamic respiratory mechanics [tidal oesophageal (P(oes,tida)l%peak) and transdiaphragmatic pressure swings (P(di,tidal)%peak) expressed as a percentage of their respective peak values] and sensory intensity and unpleasantness ratings of dyspnoea during symptom-limited incremental cycle exercise in healthy young women (n = 25) and men (n = 25). The tidal volume to forced vital capacity ratio (V(T)%FVC), breathing frequency, EMGdi%max, P(oes,tidal)%peak, P(di,tidal)%peak and sensory intensity and unpleasantness ratings of dyspnoea were higher, while dynamic inspiratory capacity and inspiratory reserve volume were lower at a standardized absolute ventilation of 55 l min(-1) during submaximal exercise in women versus men (all P < 0.05). In contrast, sex had no demonstrable effect on the inter-relationships between exercise-induced increases in V(T)%FVC, EMGdi%max and sensory intensity and unpleasantness ratings of dyspnoea. The results of this study suggest that sex differences in the intensity and unpleasantness of exertional dyspnoea in health are likely to reflect the awareness of a relatively higher neural respiratory motor drive (or EMGdi%max) needed to achieve any given ventilation during exercise in the setting of relatively greater dynamic mechanical constraints on V(T) expansion in women.