We examine the effect of fibronectin administration on mortality in sepsis. An English language literature search using MEDLINE, EMBASE, SCISEARCH, and compu terized databases of unpublished research in addition to bibliographic review was performed, and duplicate independent review of 41 articles by two observers identified six relevant randomized clinical trials. Study quality and descriptive information concerning the pop ulation, intervention, and outcome measurements were assessed. Three of six trials demonstrated favorable mor tality trends, but none reached statistical significance. Results of the 282 patients in all six trials yield a com mon odds ratio of 0.97 and a 95% confidence interval of 0.58 to 1.61. These results do not show a statistically significant effect favoring treatment, but neither do they exclude a clinically important benefit. The benefit of fibronectin in decreasing mortality in sepsis is not sup ported by these studies. However, methodological heterogeneity and the possibility of a Type II error, as well as our understanding of the role of fibronectin in the pathophysiology of sepsis, do not allow for a firm negative conclusion regarding the therapeutic efficacy of fibronectin in sepsis. A large, rigorously designed trial should be considered once investigators can reach a consensus regarding current methodological and patho physiological controversies.