An animal model implanted with intraperitoneal plastic reservoirs was used for study of the penetration of penicillin G into sites infected with Bacteroides fragilis. Penicillin G was given to rabbits, and its concentration in uninfected reservoirs and in those infected with B. fragilis was determined. The mean percentage penetration ([concentration in capsule divided by peak concentration in serum] X 100) of penicillin into uninfected capsules was 19.9%, whereas that into heavily infected capsules was 1.5%. The percentage penetration of radiolabeled penicillin into infected capsules was 12.5%, whereas the proportion of bioactive drug in the same capsules was again very low (1%). These results show that there is a modest reduction in penetration of penicillin into infected sites and a striking inactivation of the drug by B. fragilis in this experimental model.