The combination of ampicillin together with trimethoprim-sulfonamide is sometimes used as a broad-spectrum antimicrobial regimen for treatment of dogs with bacterial infections of unknown etiopathogenesis. To determine whether this combination is indeed broad spectrum, we analyzed susceptibility data derived from commonly encountered bacterial agents in dogs. A total of 381 isolates from 344 cases was studied. Overall, 80 (20.9%) of the 381 isolates were resistant to ampicillin and to trimethoprim-sulfonamide; 159 (41.7%) were resistant to ampicillin, but susceptible to trimethoprim-sulfonamide; 131 (34.4%) were susceptible to both ampicillin and trimethoprim-sulfonamide; and 11 (2.9%) were susceptible to ampicillin, but resistant to trimethoprim-sulfonamide. Of isolates susceptible to ampicillin and/or trimethoprim-sulfonamide, 290 (96.3%) were susceptible to trimethoprim-sulfonamide (ampicillin increased the coverage by 3.7%). On the other hand, 142 (47.2%) were susceptible to ampicillin. In addition, with respect to agents most commonly encountered (members of the family Enterobacteriaceae and members of the genus Staphylococcus), combining ampicillin with trimethoprim-sulfonamide increased coverage by 2.2% over use of trimethoprim-sulfonamide alone. We contend, therefore, that use of ampicillin together with trimethoprim-sulfonamide does not result in an acceptable broad-spectrum antimicrobial regimen for treatment of bacterial disease in dogs.