Mutational loss of the D2 porin causes imipenem resistance in Pseudomonas aeruginosa. It was found that this mechanism could function only when the chromosomal beta-lactamase was expressed. Mutants lacking both the beta-lactamase and the D2 porin were almost as susceptible as those that lacked the beta-lactamase but retained the porin. Thus, imipenem resistance reflected an interplay of the enzyme and impermeability, not either factor alone. These findings suggest that the activity of a carbapenem more beta-lactamase stable than imipenem should be less affected by the porin loss. Meropenem approached this behavior.