The use of non-invasive resistive breathing to task failure to assess inspiratory muscle performance remains a matter of debate. CO2 retention rather than diaphragmatic fatigue was suggested to limit endurance during inspiratory resistive breathing. Cervical magnetic stimulation (CMS) allows discrimination between diaphragmatic and rib cage muscle fatigue. We tested a new protocol with respect to the extent and the partitioning of inspiratory muscle fatigue at task failure. Nine healthy subjects performed two runs of inspiratory resistive breathing at 67 (12)% of their maximal inspiratory mouth pressure, respiratory rate (fR), paced at 18 min(-1), with a 15-min pause between runs. Diaphragm and rib cage muscle contractility were assessed from CMS-induced esophageal (P(es,tw)), gastric (P(ga,tw)), and transdiaphragmatic (P(di,tw)) twitch pressures. Average endurance times of the first and second runs were similar [9.1 (6.7) and 8.4 (3.5) min]. P(di,tw) significantly decreased from 33.1 to 25.9 cmH2O in the first run, partially recovered (27.6 cmH2O), and decreased further in the second run (23.4 cmH2O). P(es,tw) also decreased significantly (-5.1 and -2.4 cmH2O), while P(ga,tw) did not change significantly (-2.0 and -1.9 cmH2O), indicating more pronounced rib cage rather than diaphragmatic fatigue. End-tidal partial pressure of CO2 ( PETCO2) rose from 37.2 to 44.0 and 45.3 mmHg, and arterial oxygen saturation (SaO2) decreased in both runs from 98% to 94%. Thus, task failure in mouth-pressure-targeted, inspiratory resistive breathing is associated with both diaphragmatic and rib cage muscle fatigue. Similar endurance times despite different degrees of muscle fatigue at the start of the runs indicate that other factors, e.g. increases in PETCO2, and/or decreases in SaO2, probably contributed to task-failure.