Among 1429 Escherichia coli isolates collected as part of the SENTRY Antimicrobial Surveillance Program (2004) from 30 North American medical centres, 65 (4.5%) were screen-positive for an extended-spectrum beta-lactamase (ESBL). Among the strains with a negative ESBL confirmatory test (n=26; clavulanic acid inhibition), a CMY-2 enzyme was detected in 13 isolates (50.0%), FOX-5 in 3 isolates (11.5%) and DHA-1 in 1 isolate (3.8%). These AmpC-producing E. coli were cephamycin (cefoxitin)-resistant but susceptible to cefepime (minimum inhibitory concentration (MIC) < OR =0.12-4 mg/L). Clearly, the ESBL tests recommended by the Clinical and Laboratory Standards Institute identify only a fraction of E. coli with elevated beta-lactam MIC values as ESBL-producing strains; the majority of the remaining strains would be potentially responsive to some other beta-lactams, directed by accurately performed and interpreted susceptibility methods.