Emergence of resistance to imipenem during therapy for Pseudomonas aeruginosa infections is common and may result in treatment failure. Resistance emerges most often during therapy for lower respiratory tract infections. There are several unique features of this resistance to imipenem. First, cross-resistance to other beta-lactam agents is not observed. Second, the mechanism of resistance in most of the isolates studied to date appears to be related to a selective permeability barrier across the bacterial outer membrane, usually associated with discrete alterations in the electrophoretic profiles of outer membrane proteins. These data suggest that imipenem may traverse the outer membrane of P. aeruginosa via a specific porin protein that is not critical for penetration of other beta-lactam antibiotics.