BACKGROUND: To evaluate the in vitro activity of the ampicillin-sulbactam and amoxicillin-clavulanic acid against Escherichia coli isolations resistant to ampicillin and amoxicillin and the efficacy of the disks of ampicillin sulbactam 10/10 microgram and amoxicillin-clavulanic acid 20/10 micrograms to differentiate the susceptible (S) and resistant (R) isolates. METHODS: We evaluated the in vitro susceptibility of 100 consecutive clinical isolates of ampicillin and amoxicillin resistant E. coli by the broth macrodilution method and disk diffusion test against ampicillin-sulbactam and amoxicillin-clavulanic acid. RESULTS: For amoxicillin-clavulanic acid the 64% of the isolates were susceptible, 34% were moderately susceptible and 2% were resistant. In contrast, the in vitro activity of ampicillin-sulbactam was inferior since 13% of the isolates were susceptible, 24% moderately susceptible and 63% were resistant. By using the disk of ampicillin-sulbactam 10/10 microgram we found a 13% of very major errors and a 44% of minor errors when we consider the actual rules of NCCLS (R < or = 11 mm and S > or = 15 mm). The best results were achieved when we took into account zone size < or = 15 mm as R and > or = 20 mm as S; however, the level of errors was high too (25% minor errors). For the disk of amoxicillin-clavulanic acid 20/10 micrograms we found a 31% of minor errors when using the advised break points (R < or = 13 mm and S > or = 18 mm). CONCLUSIONS: We consider that the disk diffusion tests are not applicable to these combinations when E. coli isolates resistant to aminopenicillin are evaluated. We advise not to extrapolate the results of sensibility or resistance from one combination to the other because it presents a different in vitro activity.