A rabbit model was explored in preliminary studies of uterine colonization and infection, following cesarean section (CS), by toxigenic Staphylococcus aureus (Harrisburg) and other bacterial species known to be isolated from traumatized human uteri; effects on host susceptibility of fibronectin prophylaxis were studied. Histological characteristics and plasma fibronectin levels were recorded in double-blinded studies of four groups of rabbits (55 total), all sacrificed 96 h after CS performed at term. Animals which were inoculated without fibronectin prophylaxis, showed stable or slightly elevated plasma fibronectin levels through 96 h. Rabbits inoculated with nontoxigenic S. aureus (Wiley) exhibited stable fibronectin levels and less microscopic evidence of infection. All inoculated animals were colonized, but those that received fibronectin cryoprecipitate intravenously at CS showed less microscopic evidence of infection. Fibronectin levels for rabbits scores as ‘seriously infected’ were nearly 1.5 times that of controls. This is in contrast to other clinical studies in which chronic infections and poor clinical outcome have been strongly correlated with decreased plasma fibronectin levels. Histochemical studies of antifibronectin binding suggested that less fibronectin is deposited throughout the endometrial stroma of animals that received fibronectin prior to bacterial challenge. An increased polymorphonuclear leukocytic reaction in the stroma near the incisions was observed in animals that received fibronectin prophylaxis, with or without bacterial challenge. This reaction may be characterized as an acute-phase reaction.