In vitro activity of cefixime, an experimental oral third-generation cephalosporin and 7 other antimicrobials (ampicillin, augmentin, trimethoprim/sulfamethaxazole, cefamandole, cefotaxime, cefuroxime, and cefaclor) were determined for 150 isolates of Haemophilus obtained from pediatric patients. All (109) non-typeable H. influenzae isolates were sensitive to cefixime and cefotaxime. All (18) isolates of H. parainfluenzae were sensitive to cefotaxime, cefuroxime, cefamandole, cefaclor, and augmentin; 17/18 isolates were sensitive to cefixime. All (23) isolates of H. influenzae-b were sensitive to cefixime, cefotaxime, cefamandole, cefuroxime, cefaclor, and augmentin. Only 10/23 were sensitive to tri/sulfa. 137 of 150 (91.3%) isolates had MBCs equivalent to their MICs for cefixime, compared to 149/150 (99.3%) isolates for cefotaxime. Approximately 95% (143/150) of isolates tested had MICs of less than or equal to 0.06 microgram/ml for cefixime. These data demonstrate that in vitro cefixime has good activity against Haemophilus isolates and it is very similar to the activity of cefotaxime.