The ventilatory and occlusion pressure (P100) responses to hypercapnia, maximal inspiratory airway and transdiaphragmatic pressures, and the separate volume contributions of the rib cage and abdomen to tidal breathing were evaluated in 16 patients with chronic stable interstitial lung disease. Compared with those in the normal subjects, ventilation and P100 at a PCO2 = 55 mmHg were significantly higher (p less than 0.05 and p less than 0.01, respectively) in the patients with interstitial lung disease. However, the ventilatory and occlusion pressure responses to hypercapnia (delta VE/delta PCO2 and delta P 100/delta PCO2, respectively) were not significantly different between the groups. Maximal inspiratory airway pressure was significantly reduced in the patient group (p less than 0.05); maximal transdiaphragmatic pressure was also reduced but not significantly. At any given level of ventilation, tidal volume was decreased and breathing frequency increased in the patients with interstitial lung disease (p less than 0.05). The greater respiratory frequency was caused by reductions in both expiratory and inspiratory time. Because of smaller tidal volumes, rib cage expansion was reduced in the group of patients when compared with that in normal subjects during both spontaneous breathing and when compared at the same level of hypercapnia; abdomen volume was reduced to a lesser extent. We conclude that in patients with interstitial lung disease, non-chemical, presumably neural, mechanisms, increase respiratory drive and alter the breathing pattern. We speculate that both vagal mechanisms and mechanoreceptors in the chest wall sensitive to rib cage expansion contribute to these responses.