Encapsulation in Bacteroides species has been thoroughly studied in vivo as a virulence factor in abscess formation. Its pathogenic role in lethal infections caused by a mixture of pathogens has been less well investigated. Our previous studies using the rat fibrin clot peritonitis model have demonstrated lethal synergy between Bacteroides fragilis and Escherichia coli. In order to determine the synergistic role of the encapsulation of the Bacteroides component in this model, inoculations of E. coli plus one of seven Bacteroides strains of differing degrees of encapsulation were assessed for their effect on mortality. Both unencapsulated Bacteroides strains tested (B. distasonis 1244, B. vulgatus 4300) produced an early lethal synergistic effect with E. coli while the heavily encapsulated strain, B. thetaiotaomicron 1603 did not do so. The four other Bacteroides strains tested were encapsulated and their synergy with E. coli was demonstrated. Control Gram-positive strains, Streptococcus faecalis and Staphylococcus aureus, did not alter mortality when mixed with E. coli in this model. These studies support the concept that virulence factors other than encapsulation are important in the outcome of polymicrobial infections in which Bacteroides species play a part.