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An experimental animal model that stimulates the mixed aerobic-anaerobic microflora of intraabdominal sepsis was used to study antimicrobial efficacy in vivo. Treatment of infected rats with chloramphenicol resulted in only a modest reduction in the percentage of animals surviving infection with abscesses at necropsy. This unanticipated observation led to further exploration of the predominant anaerobes associated with the experimental infection. In vitro cultures of Bacteroides fragilis, susceptible to chloramphenicol in traditional tests, were capable of reducing chloramphenicol to its aryl amine derivative, which is biologically inactive. In contrast, metronidazole, an antimicrobial agent active against anaerobes, reduced the coli-metronidazole, an antimicrobial agent active against anaerobes, reduced the coli-form-associated mortality in this animal model. Subsequent studies showed that this reduction in mortality is dependent on the presence of an anaerobe and that the levels of Escherichia coli in mixed continuous culture with B. fragilis are reduced by addition of metronidazole. This reduction following addition of metronidazole was not observed either in a pure culture of E. coli or when clindamycin was added to a mixed culture. In a modification of the previously described model, infective material was placed subcutaneously into Wistar rats. Studies with this model suggested that the host's response to bacterial challenge is dependent on the site of infection and that organotropism of the implanted bacterial species is an important determinant of infection.