Physiologic adaptations after an 8-wk endurance training program were examined in 13 patients with chronic obstructive pulmonary disease (COPD) (age, 64 +/- 4 [SD] yr; FEV1, 43 +/- 9% pred; PaO2, 72 +/- 8 mm Hg; and PaCO2, 36 +/- 2 mm Hg) and in eight healthy sedentary control subjects (61 +/- 4 yr). Both pre- and post-training studies included: (1) whole-body oxygen consumption (V O2) and one-leg O2 uptake (V O2leg) during exercise; and (2) intracellular pH (pHi) and inorganic phosphate to phosphocreatine ratio ([Pi]/[PCr]) during exercise; and half-time of [PCr] recovery. After training, the two groups increased peak V O2 (p < 0.05 each) and showed a similar fall in submaximal femoral venous lactate levels (p < 0.05 each). However, control subjects increased peak V E (p < 0.01) and raised peak O2 delivery (p = 0.05), not shown in patients with COPD. Both groups increased post-training O2 extraction ratio (p < 0.05). The most consistent finding, however, was in patients with COPD, who had a substantial improvement in cellular bioenergetics: (1) half-time of [PCr] recovery fell from 50 +/- 8 to 34 +/- 7 s (p = 0.02); and (2) at a given submaximal work rate, [Pi]/[PCr] ratio decreased and pHi increased (p < 0.05 each). We conclude that beneficial effects of training in patients with COPD essentially occurred at muscle level during submaximal exercise.