The antibacterial activity of clindamycin and metronidazole against Bacteroides fragilis was quantitated in vitro by MIC determination and colony counting at 24 h and in vivo from the effects on an experimental B. fragilis infection in mice; this infection was established after co-inoculation of B. fragilis and Escherichia coli. In vitro, clindamycin was 8 to 16 times more effective than metronidazole in terms of MIC values, and more than 30 times according to colony counts at 24 h. In vivo clindamycin was almost 8 times less effective than metronidazole according to dose. This was partly due to its less favorable pharmacokinetic properties, but clindamycin was still only 1.6 times more effective than metronidazole according to free plasma concentrations. In vivo neither clindamycin nor metronidazole had any antibacterial effect against E. coli. The discrepancy between the in vivo and in vitro results for B. fragilis is discussed.