The pulmonary diffusing capacity for carbon monoxide (DLCO) is reduced in chronic heart failure and remains decreased after heart transplantation. This decrease in DLCO may depend on a permanent alteration after transplantation of one or the other of its components: diffusion of the alveolar capillary membrane or the pulmonary capillary blood volume (Vc). Therefore, we measured DLCO, the membrane conductance, and Vc before and after heart transplantation. At the time of hemodynamic measurements, the Roughton and Forster method of measuring DLCO at varying alveolar oxygen concentrations was used to determine the membrane conductance, Vc, DLCO/alveolar volume (VA), the membrane conductance/VA and thetaVc/VA (theta = carbon monoxide conductance of blood, VA = alveolar volume) in 21 patients with class III to IV heart failure before and after transplantation, and in 21 healthy controls. Transplantation normalized pulmonary capillary pressure and increased cardiac index. DLCO was decreased before transplantation (7.11 vs 10.0 mmol/min/kPa in controls), but DLCO/VA was normal (1.67+/-0.44 vs 1.71+/-0.26 mmol/min/kPa/L in controls). DLCO/VA remained unchanged after transplantation, because the decrease in Vc (82+/-30 vs 65+/-18 ml before and after transplantation) and thetaVc/VA was not compensated by the changes in membrane conductance (11+/-4 vs 12+/-5 mmol/min/kPa before and after transplantation, respectively) and membrane conductance/VA. We conclude that the decrease in DLCO in patients with chronic heart failure is due to a restrictive ventilatory pattern because their DLCO/VA remains normal; the decrease in the membrane conductance is compensated by the increase in Vc. After transplantation, the decrease in Vc due to normalization of pulmonary hemodynamics is not completely compensated for by an increase in membrane conductance. Because the membrane conductances, measured before and after transplantation, are negatively correlated with duration of heart failure, its abnormal pulmonary hemodynamics may have irreversibly altered the alveolar capillary membrane.