Quadriceps femoris muscle needle biopsies were performed in ten patients with chronic obstructive pulmonary disease and acute respiratory failure and in ten age- and sex-matched healthy control subjects. The main indices of skeletal muscle cell energy metabolism, intracellular acid-base equilibrium and lactate metabolism were evaluated. Reduced ATP and phosphocreatine content, intracellular acidosis related to hypercapnia, increased muscle lactate without alterations of the muscle lactate concentration gradient were observed in the skeletal muscle of the hypercapnic-hypoxemic COPD patients studied, in which group no correlation was found between hypoxia and energy or lactate metabolism parameters. These results suggest that an overall derangement of cell energy metabolism and acid-base equilibrium is present in severely hypercapnic-hypoxemic chronic obstructive pulmonary disease and that in this condition skeletal muscle seems to metabolize anaerobically-even though, in addition to hypoxia, other factors interfering with both cell energy and lactate metabolism are likely to be present.