The aim of this study was to determine whether an elevation of pulmonary venous pressure (PVP) and atrial natriuretic peptide (ANP) affects pulmonary vascular resistance (PVR) and pulmonary vascular incremental resistance (iPVR). We vascularly isolated the left lower lobe of the lung and perfused it with blood using a pulsatile pump. Blood flow (PBF) to the isolated lobe was decreased in 6 to 7 steps from about 8 to 1 ml/(kg.min). PVR was calculated from measurements of PBF and the pressure difference between pulmonary arterial pressure and PVP at four different levels of fixed PVP. iPVR was estimated from a slope of the pressure-flow relationships between effective pulmonary driving pressure and PBF at four different levels of fixed PVP. iPVR was 2.2 +/- 0.2, 2.2 +/- 0.1, 2.4 +/- 0.1, and 2.6 +/- 0.2 mmHg.min.kg/ml, when PVP was 0, 5, 10, and 15 mmHg, respectively. To test whether or not the response of the pulmonary vascular bed to the elevated PVP is modulated by ANP, iPVR was estimated before and after an administration of ANP in the perfusion circuit. Increased iPVR from 2.1 +/- 0.2 to 2.5 +/- 0.2 mmHg.min.kg/ml in response to the elevation of PVP from 0 to 15 mmHg decreased to the control level after the administration of ANP. ANP, however, did not change the control iPVR. PVR decreased with increasing PVP. ANP decreased PVR when PVP was 0 mmHg, but did not change it when PVP was 15 mmHg. These results suggest that ANP decreases PVR and restores the decreased pulmonary vascular compliance.