There are no reports concerning the regulation of end-expiratory lung volume (EELV) and flow-volume relationships during upper limb exercise in health and disease. We studied EELV during such exercise in 22 adults with cystic fibrosis (CF) and nine age-matched healthy control subjects. Subjects with CF were grouped according to the severity of their lung disease, as follows: mild = FEV1 > 80% predicted; moderate = FEV1 40 to 80% predicted, and severe = FEV1 < 40% predicted. EELV was calculated from measurements of inspiratory capacity (IC) made at each workload during an incremental arm and leg ergometer test to peak work capacity. In the control group, the decrease in EELV was significantly smaller for arm than for leg exercise at peak work (-0.13 L versus -0.53 L, p < 0.001) and for arm than for leg exercise at an equivalent submaximal ventilation (-0.13 L versus -0.46 L, p < 0.01). In the groups with moderate and severe CF, arm exercise resulted in an increase in EELV from resting levels (dynamic hyperinflation) that was not significantly different from the increase observed for leg exercise. For CF subjects there was a significant inverse relationship between FEV1 and changes in EELV from rest to peak arm exercise (r = -0.46, p < 0.05). In normal subjects, there was a difference in the EELV response for arm versus leg exercise. In CF subjects with airflow limitation, dynamic hyperinflation occurred with both forms of exercise.