Patients with pneumococcal pneumonia are often given fluids intravenously for hydration and maintenance of circulating blood volume. We studied the effects of plasma volume expansion on respiratory gas exchange and pneumonia size in a canine model of lobar pneumonia. Seven ventilated anesthetized dogs (Group T) with left lower lobe pneumococcal pneumonia were infused with dextran 75 in 0.9% saline solution to increase the pulmonary capillary wedge pressure to 10 mmHg for 3 h. These were compared with 7 control dogs (Group C) with left lower lobe pneumonia. Measurements of cardiac output, intrapulmonary shunt (QS/QT), and lobar distribution of perfusion were taken at baseline (B), immediately after volume infusion (V), and 3 h later (F); similar intervals were used in control animals. In Group T, QS/QT increased significantly from 24% at B to 34% at F. Part of this increase in QS/QT occurred immediately after volume infusion (29% at V) and was associated with the concomitant increase in cardiac output (4.7 L/min at B to 10.6 L/min at F). In Group C, there were no changes in cardiac output or QS/QT. At autopsy, mean wet weight for both lower lobes in Group T were greater than in Group C. Accordingly, small elevations in pulmonary capillary wedge pressure associated with fluid administration caused large increases in lobar wet weights. At least in part, these increases represented transudation of plasma and crystalloid into alveolar spaces and suggested large increases in extravascular lung liquid flux from inflamed vessels in infected lung.