The in vitro activities of Sch 34343, a new penem antibiotic, and cefbuperazone, a new cephamycin antibiotic, were determined against 459 clinical anaerobic bacterial isolates and compared with the activities of imipenem and cefoxitin, respectively, by an agar dilution method. Both penems showed potent and similar activity against all anaerobic bacteria tested, particularly Peptococcus spp., Bacteroides fragilis, and Clostridium perfringens. All organisms except a single strain of Fusobacterium necrogenes were inhibited by an 8 micrograms/ml concentration of either Sch 34343 or imipenem. Overall, gram-positive bacilli, particularly Lactobacillus species, Clostridium difficile, and Bifidobacterium and Actinomyces species, were relatively more resistant to either penem than other genera of anaerobic bacteria tested. Cefbuperazone demonstrated only modest activity against a wide spectrum of anaerobic bacteria. It had excellent and selective activity against B. fragilis and Bacteroides vulgatus but was highly inactive against Bacteroides distasonis and Bacteroides thetaiotaomicron within the B. fragilis group. Both cephamycins showed virtually no activity against C. difficile and Lactobacillus spp. Although cefbuperazone was more active against Bifidobacterium spp., it had less activity against Fusobacterium spp., Eubacterium spp., and all Bacteroides spp. other than B. fragilis and B. vulgatus.