To determine whether diaphragmatic fatigue in the intact animal subjected to loaded breathing is associated with a decrease in diaphragmatic blood flow, seven unanesthetized sheep were subjected to severe inspiratory flow resistive (IFR) loads that led to a decrease in transdiaphragmatic pressure (Pdi) and a rise in arterial PCO2 (PaCO2). Blood flow to the diaphragm, other respiratory muscles, limb muscles, and major organs was measured using the radionuclide-labeled microsphere method. With these loads blood flow increased to the diaphragm (621 +/- 242%) and all the other inspiratory and expiratory diaphragm (621 +/- 242%) and all the other inspiratory and expiratory muscles; there was no statistically significant change in blood flow to these muscles at the time when Pdi decreased and PaCO2 rose. Blood flow also increased to the heart (103 +/- 34%), brain (212 +/- 39%), and adrenals (76 +/- 9%), whereas pancreatic flow decreased (-66 +/- 14%). Limb muscle blood flow remained unchanged. We conclude that in unanesthetized sheep subjected to IFR loads 1) we did not demonstrate a decrease in respiratory muscle blood flow associated with diaphragmatic fatigue and ventilatory failure, and 2) there is a redistribution of blood flow among major organs.