Recently, it was suggested that fatigue of peripheral muscles could contribute to exercise limitation in patients with chronic obstructive pulmonary disease (COPD). In order to quantify the role of peripheral muscle force, we restudied potential determinants of exercise capacity (6-min walking distance [6 MWD] and maximal oxygen consumption [over dotVO(2)max]) in 41 consecutive COPD patients (FEV(1), 43 +/- 19% of predicted, TL(CO), 56 +/- 25% of predicted) admitted to our pulmonary rehabilitation program. over dot VO(2)max (incremental cycle ergometer test), 6 MWD (best of three), lung function (FEV(1), FVC, TLC, FRC), diffusing capacity (TL(CO)), isometric quadriceps force (QF), hand grip force (HF), and maximal inspiratory (PImax,) and expiratory (PE(max)) pressures were measured. Patients had a poor 6 MWD (372 +/- 136 m) and over dot VO(2)max (1.35 +/- 0.60 L, 71%), reduced respiratory (PImax 65 +/- 27%) and peripheral muscle force (QF 74 +/- 27%, HF 82 +/- 23%). In single regression analysis, significant correlations (r) were found for over dot VO(2)max and TL(CO) (0.68), FEV(1) (0.64), QF (0.55), HF (0.53), and body weight (0.49). Walking distance was significantly correlated with QF (0.63), HF (0.61), PImax (0.49), and TL(CO) (0.38). In stepwise multiple regression analysis, the variables significantly contributing to 6 MWD were QF and PImax. For over dot VO(2)max, variables significantly contributing were TL(CO), QF, and FEV(1). We conclude that lung function and peripheral muscle force are important determinants of exercise capacity in COPD.