Plasma fibronectin deficiency and opsonic dysfunction exist in critically ill septic surgical, trauma, and burn patients with multiple organ failure. Fibronectin deficiency can be reversed by infusion of fresh plasma cryoprecipitate. The influence of therapy with human cryoprecipitate on lung vascular permeability in septic sheep with plasma fibronectin deficiency following surgery was evaluated. Additionally, selected studies on pulmonary function in septic surgical and trauma patients after infusion of plasma cryoprecipitate were completed. In patients, ventilation-perfusion balance appeared to improve as measured by the multiple inert gas elimination technique. With the lung lymph fistula preparation in fibronectin deficient sheep, infusion of human plasma cryoprecipitate (10 units; 250 ml) delayed the onset and minimized the increase in lung vascular permeability during postoperative Pseudomonas sepsis (5 X 10(9) bacteria, I.V.; 5 X 10(10) bacteria, I.P.). For example, in a first group of sheep, the transvascular protein clearance (TPC) at 2 hrs in septic sheep (n = 4) treated with only saline (volume control) was 20.1 +/- 3.1 ml/hr, compared to 11.23 +/- 0.83 ml/hr in the sheep (n =a 4) treated with fibronectin-rich cryoprecipitate (p less than 0.05). In a second group of sheep, cryoprecipitate depleted of fibronectin by affinity chromatography was used as the control solution. It also did not manifest this protective effect with respect to lung vascular permeability. Thus, at 2 hrs the lymph flow (Qlym) was 30.2 ml/hr and the transvascular protein clearance (TPC) was 18.0 ml/hr in septic sheep given fibronectin-deficient cryoprecipitate. In contrast, in the fibronectin-rich cryoprecipitate treated sheep, the Qlym was 14.8 ml/hr and the TPC was 8.12 ml/hr. It is suggested that fibronectin may influence lung vascular integrity during sepsis following surgery and trauma.