Known numbers of standard strains of Escherichia coli and Bacteroides fragilis were inoculated together into surgical incision in guinea-pigs. Histological and quantitative bacteriological proof is presented that pathogenic synergy occurred in vivo with copious pus formation when combinations of subinfective doses of each organism were inoculated. A further series of experiments showed that the amounts and ratios of E. coli and B. fragilis in the septic inocula were critical, and that the resultant pus contained equal numbers of both the aerobic and the anaerobic organisms. This model may be suitable for the experimental validation of short-term regimens of prophylactic antibiotics in surgery; the present results seem to have important therapeutic implications.