The National Committee for Clinical Laboratory Standards agar dilution method was used to compare the in vitro activity of WY-49605 (also called SUN/SY 5555 and ALP-201), a new broad-spectrum oral penem, to those of amoxicillin, amoxicillin-clavulanate, imipenem, ciprofloxacin, cefaclor, cefpodoxime, cefuroxime, clindamycin, and metronidazole against 384 clinically isolated anaerobes. These anaerobic organisms included 90 strains from the Bacteroides fragilis group, 87 PrevoteUla and Porphyromonas strains, non-B. fragilis group Bacteroides strains, 56 fusobacteria, 55 peptostreptococci, 49 gram-positive non-spore-forming rods, and 47 clostridia. Overall, VVY-49605 had an MIC range of 0.015 to 8.0 ,ig/ml, an MIC at which 50% of the isolates are inhibited (MIC50) of 0.25 ,ig/ml, and an MIC at which 90% of the isolates are inhibited (MIC90) of 2.0 ,ug/ml. Good activity against all anaerobe groups was observed, except for Clostridium diJficik and lactobacilli (MIC,0s of 4.0 and 2.0 ,ug/ml, respectively, and MIC90s of 8.0 and 2.0 ,ug/ml, respectively). Imipenem had an MWIC50 of 0.03 ,ug/ml and an MIC90 of 0.25 ,Lg/ml. Ciprofloxacin was much less active (MIC_o of 2.0 ,ug/ml and MIC90 of 16.0 ,ug/ml). By comparison, all oral ,I-lactams were less active than WY-49605, with susceptibilities as follows: amoxicillin MIC_o of 8.0 ,Ig/ml and MIC90 of >256.0 ,ug/ml), amoxicillin-clavulanate MIC50 of 1.0 ,Ig/ml and MIC90 of 8.0 ,ug/ml, cefaclor MIC50 of 8.0 ,ug/ml and MIC90 of >32.0 ,ug/ml, cefpodoxime MIC_0 of 4.0 ,ug/ml and MIC90 of >32.0 ,ug/ml, and cefuroxime MIC50 of 4.0 ,ug/ml and MIC90 of >32.0 jig/ml.Clindamycin was active against all groups except some members of the B.fragilis group, Fusobacterium varium, and some clostridia (overall MIC50 of 0.5 ,ug/ml and overall MIC90 of 8.0 ,ug/ml). Metronidazole was active (MIC of <4.0 ,Ig/ml) against all gram-negative anaerobic rods, but most gram-positive non-spore-forming rods, some peptostreptococci, and some clostridia were less susceptible. To date, WY-49605 is the most active oral ,-lactam against anaerobes: these results suggest clinical evaluation for clinical indications suitable for oral therapy.