In vitro cefditoren antimicrobial activity was tested by broth microdilution and disk diffusion methods against 300 Streptococcus pneumoniae and 299 Haemophilus influenzae isolates. MICs were also determined for three comparison drugs. The MICs of cefditoren were very comparable to those of cefotaxime against both species. If penicillin-resistant pneumococci are to be considered not susceptible to cefditoren, the tentative MIC breakpoints for cefditoren of < or = 0.25 microg/ml for susceptible and > or 1.0 microg/ml for resistant could be selected. With these breakpoints, all penicillin-susceptible pneumococci were cefditoren-susceptible, as were 85% of penicillin-intermediate strains. Provisional zone diameter breakpoints would be > or = 26 mm for susceptible and < or = 20 mm for resistant. If penicillin-resistant pneumococcal infections are shown to clinically respond to cefditoren therapy, then a susceptible MIC breakpoint of < or = 1.0 microg/ml would be appropriate, with a corresponding zone diameter breakpoint of > or = 21 mm. A susceptible MIC breakpoint of < or = 0.5 or < or = 1.0 microg/ml is appropriate for H. influenzae, but lack of correlation between cefditoren MICs and disk diffusion zone diameters when testing H. influenzae leads us to make no recommendations at this time regarding cefditoren disk tests for H. influenzae.