Ventilatory mechanics were measured at rest and during steady-state (25%, 50%, 75%) and maximal exercise (W-Max) on a cycle-ergometer in eight adult patients (FEV1 22 to 114% of predicted) with cystic fibrosis (CF). Tidal flow-volume loops were measured at rest and during exercise and placed within the maximal pre- and postexercise flow-volume loops, based on measured end-expiratory lung volume (EELV). The degree of flow limitation was expressed as the percentage of the tidal flow-volume loop that met the expiratory boundary of the maximal loop (TFVL%). Pressure-volume relationships were assessed by measurement of transpulmonary pressure (PTP). Peak inspiratory PTP was compared with maximal inspiratory pressures at rest and during exercise (Pcap(i)) at the equivalent lung volume. The maximal effective expiratory pressure (Pmax(e)) was determined using the orifice technique. Three patients with milder disease (FEV1 114, 98, 89% of predicted) did not show any flow limitation at rest or 50% W-Max but two did show some flow limitation at W-Max (0, 3, 23 TFVL%) with a decrease in EELV (-400, -200, -300 ml). There was considerable reserve for inspiratory and expiratory pressure generation at W-Max. Flow limitation was noted at rest in three patients and at 50% W-Max in the five patients with more severe airways obstruction. The increased flow was achieved by an increase in EELV in all five patients (+400, +430, +330, +150, +700 ml at W-Max). Pcap(i) was reached in two patients (-28, -36 cm H2O), while Pmax(e) was exceeded by four patients suggesting inefficient pressure generation. Expiratory flow limitation, hyperinflation, and pressure swings approaching capacity severely compromised the capacity to generate ventilation in some patients with CF.