The development of fatigue was investigated in the diaphragm of anaesthetized, tracheostomized, spontaneously breathing cats during restricted air flow. Ventilation, transdiaphragmatic pressure (Pdi), integrated electrical activity of diaphragm (Edi) and phrenic nerve (Eph) were measured simultaneously and expressed as a percentage of values at unloaded breathing. Inspiratory loads were 60, 70 and 80% of Pdi max. The Pdi max was measured by airway occlusion at functional residual capacity. The duration of loads was 40-60 min. The diaphragmatic fatigue developed only during heavy inspiratory loading (80% Pdi max). During the first 10 min of heavy load Pdi, Edi and Eph increased to 905 +/- 60%, 248 +/- 20% and 229 +/- 24%, respectively (P < 0.01), and then began to fall gradually. Ventilation declined to 39 +/- 3% after 60 min of heavy load (P < 0.01), resulting in acute hypercapnia and hypoxia. Initial fatigue appeared as a decrease in Pdi (to 781 +/- 63%) and parallel decline in Edi (to 233 +/- 21%) after 30 min of load (P < 0.05). Phrenic nerve activity did not change during this stage. These data suggest a peripheral basis of diaphragmatic fatigue, related to disorders in neuromuscular transmission. After 60 min of heavy load, Pdi fell to 675 +/- 49%, Edi declined to 209 +/- 28% and Eph decreased to 189 +/- 25%. We interpret the decrease in phrenic nerve activity as a weakening of central inspiratory drive and development of the central component of diaphragmatic fatigue in the last stage.