In acute myocardial infarction (AMI) alveolar interstitium edema is generally attributed to hydrostatic imbalance. However, inflammatory burden and/or neural/hormonal/hemodynamic stimulation might injure the microvascular endothelium, eliciting interstitial overflow and altering alveolar-capillary gas diffusion. In 118 patients with AMI, ejection fraction 50% and wedge pulmonary pressure <16 mmHg, admission alveolar-capillary gas diffusing membrane conductance (DM) averaged 35.1 mL . min^-1 · mmHg^-1 and was 27% lower than in 25 controls (p<0.01). Infusion of saline in the pulmonary circulation (to test sodium exchange across the pulmonary capillary wall) lowered DM by 7.1% (p<0.01) and was neutral in controls. At 1 week, 83 patients that showed DM improvement > 5% were assigned to group 1, and 28 patients with DM worsening > 5% composed group 2. Saline retained efficacy in group 2 and had no DM effect in group 1 (supporting a link between changes in baseline DM and those in microvascular salt exchange). Ventricular function was unchanged in group 1, whereas group 2 had developed diastolic dysfunction. At 1-year, 3% of cases in group 1 and 37% in group 2 had alveolar edema. Thus, AMI is frequently associated with abnormal pulmonary microvascular sodium transport/water conductance that, in case of ventricular dysfunction supervenience, may persist and worsen the outcome. In 37 AMI similar patients and in 11 control subjects, NO overexpression with L-arginine improved baseline DM and in AMI patients prevented DM reduction by saline, suggesting a mechanistic role of an impaired NO pathway in the microvascular barrier dysfunction.