We evaluated 12 patients with stable chronic airflow obstruction (CAO) and no clinical evidence of left ventricular disease to determine the effects of oral digoxin on exercise capacity (VO2 max) and on right ventricular pump function during exercise. In this randomized, double blind, placebo controlled, cross-over study, patients performed exercise tests and underwent measurement of ejection fractions after two weeks of therapy with oral digoxin (0.25 mg/day) and after two weeks of placebo. Incremental upright exercise testing to a symptom-limited maximum was performed on a cycle ergometer. Right and left ventricular ejection fractions (RVEF, LVEF) were obtained in the supine position at rest and at approximately 75 percent of the maximum workload by gated equilibrium radionuclide angiography. All patients had abnormal right ventricular function, manifested either by a low resting RVEF (less than 45 percent) or a subnormal response to exercise (less than 5 percent increase). The small increases in RVEF with digoxin (mean +/- SE) at rest (44 +/- 5 vs 41 +/- 4 percent) and during exercise (46 +/- 4 vs 44 +/- 3 percent) did not achieve statistical significance. With digoxin, small increases in exercise duration (10.0 +/- 1.5 vs 9.0 +/- 1.4 min), maximum workload achieved (48 +/- 6 vs 42 +/- 5 W), VO2 max (0.85 +/- 0.06 vs 0.81 +/- 0.06 L/min), and oxygen-pulse (O2-P) (6.6 +/- 0.5 vs 6.3 +/- 0.4 ml/beat) occurred. Only the increase in O2-P was significant (p less than 0.05). From this study we conclude that digoxin does not significantly improve exercise capacity in severe chronic airflow obstruction with impaired right ventricular function, nor does it improve RVEF either at rest or during supine submaximal exercise.