The objective of the study was to determine the direct actions of sodium nitroprusside (SNP) on the pulmonary vasculature actively constricted by hypoxic ventilation in the closed-chest dog. In 21 supine anesthetized (pentobarbital sodium, 25 mg/kg) dogs the left lower lobe was catheterized with a 20 F wedged-flow catheter. With constant flow to this lung lobe, lobar pulmonary artery pressure (PAP), left ventricular end-diastolic pressure (LVEDP), and lobar pulmonary vascular resistance (PVR) were studied during room air and 10% O2 mechanical ventilation. With lobar flow and LVEDP constant, observed changes of lobar PAP and PVR represent direct effects on vascular tone unaffected by passive factors. Ventilation with 10% O2 resulted in a significant increase in lobar PAP [12.2 +/- 1.6 to 17.2 +/- 1.2 (SE) Torr] and PVR [42.2 +/- 13.3 to 61.2 +/- 15.0 (SE) Torr X 1(-1) X min]. Then during continued hypoxia in 12 animals, femoral vein infusion of SNP at doses of 1, 2, and 5 microgram X kg-1 X min-1 resulted in significant decreases in lobar PAP to 14.8 +/- 1.5, 14.8 +/- 1.5, and 13.4 +/- 1.6 Torr, respectively, and in PVR to 56.7 +/- 14.1, 54.0 +/- 13.9, and 47.8 %/- 13.2 Torr X 1(-1) X min, respectively. In six animals the sequence of drug infusion was then reversed with similar results. It is concluded that the actively constricted pulmonary vascular bed is directly dilated by SNP infusion.