We report the first direct measurements of the effect of pulmonary vascular pressures on perialveolar interstitial pressures. In seven experiments we varied the intravascular pressure (Pvas) in isolated dog lungs held at constant airway pressure (PA). By the micropuncture servo-null technique, we recorded perialveolar interstitial pressures with respect to pleural pressure (0 cmH2O) at the alveolar junctions (Pjct) and in microvascular adventitia (Padv). At PA = 7 cmH2O, increase from 5 to 15 cmH2O did not affect Pjct, although it decreased Padv by 1.2 +/- 0.4 cmH2O. The Pjct-Padv gradient increased by 77%. Increasing Pvas to 25 cmH2O had no further effect on either interstitial pressure. In four experiments we also determined interstitial pressure in the hilum (Phil). When Pvas was increased from 5 to 15 cmH2O, Phil increased by 4.5 +/- 0.9 cmH2O. Further elevation of Pvas to 25 cmH2O increased Phil further by 2.4 +/- 0.4 cmH2O. At PA = 15 cmH2O, all interstitial pressures decreased, but their responses to Pvas were similar. We conclude that increase of Pvas 1) increases Phil but not perialveolar interstitial pressures and 2) increases the perialveolar interstitial pressure gradient, which may promote local liquid clearance.