The present study was performed to determine the effects of pretreatment with purified human plasma fibronectin (FN) on survival in rats challenged withSalmonella typhimuriumperitonitis or E.coliendotoxemia. The effects on survival of combining FN with immunoglobulin G (IgG) or antithrombin-III (AT-III) were also determined duringS. typhimuriumperitonitis and E.coliendotoxemia. Permanent survival was increased 15% in the peritonitis group (p< 0.05) and 15% in the endotoxemic group (p > 0.05). There was no enhancement in survival by combining FN with a subprotective dose of IgG preparation. AT-III alone increased survival by 50% over survival in the control group. Combining FN with AT-III increased survival 10% greater than with AT-III alone, which is suggestive of an additive effect. Results from this study suggest that FN provides modest protection during Gram-negative peritonitis or endotoxemia in the rat. Combining FN with AT-III may augment in an additive manner the marked increase in survival observed with AT-III alone in this and previous studies.