The disk diffusion zones and the MICs of six newer antimicrobials with significant activity against Haemophilus influenzae were compared using the Haemophilus test medium (HTM) and National Committee for Clinical Laboratory Standards methods. The rank order of potency was cefpodoxime (MIC50, less-than-or-equal-to 0.03 mug/ml)> cefetamet > cefdinir > cefdaloxime = trospectomycin > cefmetazole (MIC50, 2 mug/ml). Susceptible breakpoint interpretive criteria for HTM tests were established that conformed to prior recommendations for each drug when tested against other species. Absolute agreement between methods ranged from 89% to 100% with less-than-or-equal-to 1% false-susceptible interpretive errors. The recommended, tentative disk diffusion susceptible interpretive criteria were for 5-mug cefdinir disks greater-than-or-equal-to 20 mm (MIC correlate, less-than-or-equal-to 1 mug/ml); for 10-mug cefetamet disks greater-than-or-equal-to 18 mm (MIC correlate, less-than-or-equal-to 4 mug/ml); for 30-mug cefetamet disks greater-than-or-equal-to 21 mm (MIC correlate, less-than-or-equal-to 4 mug/ml); for 30-mug cefmetazole disks greater-than-or-equal-to 16 mm (MIC correlate, less-than-or-equal-to 16 mug/ml); for 10-mug cefpodoxime disks greater-than-or-equal-to 21 mm (MIC correlate, less-than-or-equal-to 2 mug/ml); for 30-mug cefdaloxime disks greater-than-or-equal-to 23 mm (MIC correlate, less-than-or-equal-to 2 mug/ml) and for 30-mug trospectomycin disks greater-than-or-equal-to 17 mm (MIC correlate, less-than-or-equal-to 16 mug/ml). Beta-lactamase-negative, ampicillin-resistant (BLNAR) H. influenzae isolates consistently had the highest MICs for each cephalosporin tested. These BLNAR strains most influenced the perceived in vitro spectrum of each beta-lactam tested and required a recommendation of intermediate and resistant categories for cefdinir, cefetamet, and cefdaloxime.