Erythromycin and cefamandole have exhibited synergistic activity against eight strains ofBacteroides fragilis subsp. fragilis. In concentrations of only 0.25 to 0.5 ,ug of erythromycin per ml (easily obtainable with oral therapy), less than 0.4 ,g (0.015 to 1.0) ofcefamandole per ml inhibited the B. fragilis strains. In the presence of the erythromycin, the potency of cefamandole was increased more than 100-fold. On the basis of the mechanism of action of these two antibiotics, the synergism may be related to inhibition of beta-lactamase formation by the erythromycin, removal of the bacterial cell wall by the cefamandole permitting erythromycin penetration to the ribosomal level, and decreasing inoculum effect.