The effect of 2 weeks oral digoxin administration on respiratory muscle performance (RMP) in 14 patients with chronic obstructive lung disease (COPD) was investigated in a randomized double-blind placebo-controlled cross-over study. All patients were ambulatory with severe air flow obstruction. FEV1/FVC was 0.44 +/- (SD) 0.11, FEV1 was 0.88 +/- (SD) 0.35 liter/s RMP was assessed by measuring maximal inspiratory pressure (PImax), maximal expiratory pressure (PEmax), and maximal voluntary ventilation. Although these parameters were significantly reduced in the COPD patients, 2 weeks of digoxin administration (with serum levels in the therapeutic range) did not alter any parameter of RMP or spirometry. We conclude that digoxin has no effect on RMP or spirometry in ambulatory patients with severe COPD.