In view of the recent advances in our understanding of the pathophysiology of COPD, we felt that it would be appropriate to examine the contribution of several abnormalities, not hitherto examined, to exercise limitation in this disease. These included: (1) The ability to exceed maximum expiratory flow (determined during forced maneuvers from TLC) during partial expiratory maneuvers. This is referred to as deltaFEV1. (2) Shape of the flow-volume curve (Shape). (3) Susceptibility to develop dynamic hyperinflation (dynamic hyperinflation index, DHI). (4) Ventilatory response to exercise (VEmax/VEpred). Twenty-four COPD patients (FEV1 = 42 +/- 13% pred) underwent symptom-limited progressive exercise. DeltaFEV1, shape, DHI and VEmax/VEpred were determined. All values were normalized to eliminate the effects of age, sex, and body size. Shape had no impact on peak VO2 (r = 0.8). DeltaFEV1 (r = 0.50), DHI (r = 0.50) and VEmax/VEpred (r = 0.46) correlated significantly with peak VO2 with all three exceeding FEV1 (r = 0.43). DHI and deltaFEV1 correlated significantly with each other (r = 0.43) suggesting that the latter exerts its beneficial effects by reducing the tendency to develop DH. We conclude that variability among patients in ventilatory response to exercise and in deltaFEV1 (likely an expression of extent of regional mechanical heterogeneity) contribute importantly to variability of exercise tolerance in COPD.