There is evidence that female athletes may be more susceptible to exercise-induced arterial hypoxemia and expiratory flow limitation and have greater increases in operational lung volumes during exercise relative to men. These pulmonary limitations may ultimately lead to greater levels of diaphragmatic fatigue in women. Accordingly, the purpose of this study was to determine whether there are sex differences in the prevalence and severity of exercise-induced diaphragmatic fatigue in 38 healthy endurance-trained men (n = 19; maximal aerobic capacity = 64.0 +/- 1.9 ml x kg(-1) x min(-1)) and women (n = 19; maximal aerobic capacity = 57.1 +/- 1.5 ml x kg(-1) x min(-1)). Transdiaphragmatic pressure (Pdi) was calculated as the difference between gastric and esophageal pressures. Inspiratory pressure-time products of the diaphragm and esophagus were calculated as the product of breathing frequency and the Pdi and esophageal pressure time integrals, respectively. Cervical magnetic stimulation was used to measure potentiated Pdi twitches (Pdi,tw) before and 10, 30, and 60 min after a constant-load cycling test performed at 90% of peak work rate until exhaustion. Diaphragm fatigue was considered present if there was a >or=15% reduction in Pdi,tw after exercise. Diaphragm fatigue occurred in 11 of 19 men (58%) and 8 of 19 women (42%). The percent drop in Pdi,tw at 10, 30, and 60 min after exercise in men (n = 11) was 30.6 +/- 2.3, 20.7 +/- 3.2, and 13.3 +/- 4.5%, respectively, whereas results in women (n = 8) were 21.0 +/- 2.1, 11.6 +/- 2.9, and 9.7 +/- 4.2%, respectively, with sex differences occurring at 10 and 30 min (P < 0.05). Men continued to have a reduced contribution of the diaphragm to total inspiratory force output (pressure-time product of the diaphragm/pressure-time product of the esophagus) during exercise, whereas diaphragmatic contribution in women changed very little over time. The findings from this study point to a female diaphragm that is more resistant to fatigue relative to their male counterparts.