In closed chested, pentobarbitol anesthetized dogs, we studied the relationship between pulmonary vascular resistance index (PVRI) and progressively increasing positive end-expiratory pressure (PEEP) in both normal and abnormal lungs; we correlated these PEEP-induced PVRI changes with those in other pulmonary vascular and airway dynamic function indices. We continuously measured cardiac output (Qt) and pulmonary artery, left atrial, airway, and pleural pressures and intermittently measured arterial and mixed venous blood gas tensions and static and dynamic compliance (CSTA, CDYN) with an 18 ml/kg test inflation. Normal lung was converted to abnormal lung by the administration of oleic acid intravenously plus HCl intratracheally. We found that PVRI was a "U"- or "J"-shaped function of increasing PEEP in both normal and abnormal lungs. PVRI correlated inversely with cardiac index and systemic oxygen transport index and positively with the difference between pulmonary artery diastolic and left atrial pressures in both normal and abnormal lungs as well as inversely with CSTA in normal lungs. The various maxima and minima correlates of minimal PVRI occurred at PEEP of 5 cm H2O in normal lungs and PEEP of 10 cm H2O in abnormal lungs. These latter findings support the hypothesis that there is one lung volume in both normal and abnormal lungs which is optimal for ventilation, blood flow, and transport of oxygen to the tissues. These findings suggest that clinical studies should be undertaken to examine whether minimal PVRI may be used as another variable by which to titrate the application of PEEP in humans.