In vitro susceptibility of 185 penicillin-susceptible and -resistant pneumococci to WY-49605, a new oral penem, was compared with susceptibility to penicillin G, amoxicillin with and without clavulanate, cefixime, cefaclor, cefpodoxime, cefuroxime, and cefdinir. WY-49605 yielded MICs for 50 and 90% of the strains tested (MIC(50) and MIC(90), respectively) of 0.03 and 0.06, 0.125 and 0.5, and 0.5 and 1.0 mu g/ml, respectively, against penicillin-susceptible, intermediately resistant, and fully resistant strains, respectively. The MIC(50) and MIC(90) for both amoxicillin and amoxicillin-clavulanate were identical and approximately 1 doubling dilution higher than those for WY-49605 and were less than or equal to 0.06 and 0.125, 0.25 and 1.0, and 1.0 and 1.0 mu g/ml, respectively. Cephalosporin MIC(90)s were all significantly higher than those of the latter three compounds for intermediately resistant and fully resistant strains.