The diaphragmatic force generation and electromyographic response to long-term (1 h) inspiratory resistive loading was examined in the newborn piglet during the 3rd postnatal wk of life. Minute ventilation decreased to approximately 50% of baseline level within 5 min of imposition of a severe resistive load and remained at this level for the duration of loading. The decrease in ventilation was secondary to a fall in tidal volume at a constant frequency. There was a significant increase in central nervous system output to the diaphragm as manifested by integrated diaphragmatic electromyogram. Progressive augmentation of this index of central drive continued throughout the period of loading. Functional residual capacity fell significantly by 60 min of inspiratory resistive loading. This strategy should allow greater force generation by placing the diaphragm at a more optimal length-tension relationship. However, the force generating capability of the diaphragm was compromised as assessed by force frequency curve analysis. These results suggest that the diaphragm of the neonatal piglet fatigues during prolonged inspiratory resistive loading.