In nine newborn infants we looked for evidence of diaphragmatic muscle fatigue by analysis of the EMG frequency spectrum. We measured the diaphragmatic EMG with surface electrodes, the motion of the rib cage and abdomen with magnetometers, and monitored the sleep state using EEG, EOG, and behavioral criteria. Spectral frequency analysis of EMG signals, uncontaminated by ECG artifact, was subsequently performed by digital computer. In six normal infants, when we compared breaths with rib cage distortion to undistorted breaths we found the characteristic changes of fatigue in the EMG spectrum: A fall in the high-frequency (>160-640 Hz) power and an increase in the low-frequency (10-40 Hz) power. The fall in the high-to-low frequency ratio was progressive with increasing distortion (all r > 0.60, P < 0.01) and with increasing amplitude of the diaphragmatic EMG (all r > 0.65, P < 0.05). Three other infants had just come off the ventilator and were on continuous positive end-expiratory pressure at the time of the study. Two of these deteriorated and when they again required assisted ventilation, the EMG spectrum showed a significant drop in the high-to-low frequency ratio (P < 0.005). The one infant that did well off the ventilator showed no evidence of diaphragmatic fatigue. We conclude that respiratory muscle fatigue does occur even in normal infants whenever there is significant distortion of the rib cage, i.e., during active sleep, and that it plays a significant role when there is superimposed lung disease.