This report describes a patient with nosocomial meningitis from whom four distinct isolates of Enterobacter aerogenes were recovered over a complicated course of chemotherapy. The initial isolate was susceptible to expanded spectrum beta-lactams despite constitutive production of high levels of beta-lactamase. Resistant isolates recovered during antibiotic therapy had lost a 42,000 outer membrane protein. These data suggest that b-lactam susceptibility in the original isolate was due to "hyperpermeability" mediated by the 42,000 Dalton protein.