Lung microvascular permeability in sheep increases during Pseudomonas bacteremia. The sheep's low plasma opsonic fibronectin concentration and associated inefficient reticuloendothelial clearance of blood-borne particulates may contribute to the response of increased lung vascular permeability during sepsis. The present study investigated the influence of sepsis on lung fluid balance in sheep with and without opsonic glycoprotein (plasma fibronectin) deficiency. Using the lung lymph fistula preparation in sheep, we made measurements of lung lymph flow (QLYM), lymph-to-plasma protein concentration ratios (L/P), pulmonary hemodynamics, and extravascular lung water content. Deficiency of opsonic fibronectin resulted in a minimal increase in lymph flow with no change in transvascular protein clearance (QLYM X L/P). Pseudomonas sepsis with or without fibronectin deficiency resulted in a stable L/P and a transient increase in pulmonary arterial pressure, which declined to a new steady state. Although sepsis resulted in a 100% elevation (P < 0.05) in lymph flow and transvascular protein clearance, sepsis in the presence of fibronectin deficiency induced a sustained 300--400% increase in lymph flow and a 300% increase in transvascular protein clearance. Thus opsonic fibronectin deficiency exaggerates the increased lung vascular permeability during sepsis.