For wild-type bacteria the activity of biapenem was similar to that of imipenem, but for 51 imipenem-resistant strains meropenem was more active than either. When penicillin-binding protein 2a (PBP 2a) was expressed in Staphylococcus aureus biapenem had reduced activity. Mutant bacteria with decreased susceptibility to biapenem were selected in agar. Most of the mutant Gram negative bacteria were unstable and readily reverted to susceptible. The mutant Proteus vulgaris and Pseudomonas aeruginosa lacked an outer membrane protein. Biapenem-resistant S. aureus could be selected only from MRSA.