Maximal voluntary drive to the diaphragm and a non-respiratory muscle group (elbow flexors) was compared in 10 control subjects and 11 asthmatics who were studied when well. The degree of voluntary activation during repeated attempted maximal quasi-static efforts was determined using the twitch interpolation technique in the absence of contractile fatigue under both control conditions and following bronchial challenge with histamine. Diaphragm activation was assessed using bilateral phrenic stimulation at the normal resting end-expiratory lung volume after exhalation from TLC. Asthmatic subjects showed lower and more variable voluntary activation than control subjects for both diaphragm (82.0% +/- 18.4 [SD], vs 87.8% +/- 12.0, P < 0.01) and elbow flexors (91.3% +/- 7.6 vs 95.8% +/- 4.1, P < 0.01). Histamine challenge decreased FEV1 in asthmatic subjects to 50% of the initial value, but had no significant effect on voluntary activation in either subject group. The decreased voluntary drive to the diaphragm observed in some asthmatic subjects may predispose to rapid development of ventilatory failure during severe airway narrowing.