The efficacy of prophylaxis by intraperitoneal injection of gentamicin, metronidazole or both drugs combined was investigated in a mouse model of mixed infection with Escherichia coli and Bacteroides fragilis. A three dose prophylactic regimen given 12 hourly was studied starting simultaneously with bacterial challenge. Serum antibiotic concentrations lay within the human therapeutic ranges. Metronidazole alone eliminated B. fragilis from the developing infections, but at higher challenge doses the mice developed abscesses which contained E. coli, and mortality was no different from controls. Gentamicin alone eliminated both bacteria and deaths in all infections, but sterile abscesses occurred in two of five animals at the highest challenge dose. Mixed metronidazole + gentamicin abolished all effects of the challenge bacteria, aborting all infections for all challenge doses with no formation of sterile abscesses. It is proposed that, in abdominal surgery, although metronidazole or gentamicin may be effective given alone for low levels of contamination, for higher levels (e.g. colonic surgery) both drugs may be required.