Conductance of alveolar capillary membrane (DM) and capillary blood volume (VC) are the subcomponents of the pulmonary diffusing capacity for carbon monoxide (DLCO). In chronic heart failure, stress failure of the membrane provides a mechanism for reduced DM and subsequent impairment of DLCO. Angiotensin-converting enzyme inhibition improves DLCO in patients with chronic heart failure. This study was aimed at investigating which of the two subcomponents of DLCO is affected by angiotensin-converting enzyme inhibitors. Twenty-seven patients with NYHA class II to III chronic heart failure (group 1) and 13 age- and sex-matched normal subjects underwent pulmonary function testing with determination of DM and VC, while receiving placebo and 48 h and 1 and 2 months after starting enalapril treatment (10 mg twice daily). Nine similar patients (group 2) received isosorbide dinitrate (40 mg thrice daily) for a month then enalapril for another month, and underwent pulmonary function testing at 48 h and 1 month after starting treatments. Effects of angiotensin-converting enzyme inhibition in normal controls were not significant in the short- or mid-term. In group 1 patients, the only change observed at 48 h was a reduction in VC (probably due to a decrease in capillary pulmonary pressure). There was a marked increase in DM to a similar extent at 1 and 2 months, resulting in a significant improvement in DLCO despite a decrease in VC. In group 2 patients, nitrates failed to improve DLCO and DM, whereas enalapril was as effective as in group 1. These observations suggest a modulatory effect of angiotensin-converting enzyme inhibition on the membrane function which emerges gradually and persists over time and is probably dissociated from changes in pulmonary capillary pressure and VC. Chronic heart failure disturbs the alveolar capillary interface and increases gas diffusion resistance; angiotensin-converting enzyme inhibition restores the diffusive properties of the membrane and gas transfer, and protects the lung when the heart is failing.