Representative antimicrobial drugs were examined under aerobic and hypercapnic (3 and 5% v/v CO2) incubation with the Bauer-Kirby agar disk diffusion, a broth microdilution method, and the agar dilution procedure against nonfastidious, standard ATCC quality control strains and against two β-hemolytic streptococcal, two pneumococcal, and three Haemophilus influenzae ATCC strains. It was found that an atmosphere of 3-5% CO2 merely antagonized amikacin, gentamicin, and netilmicin; the activity of penicillin G was antagonized only against Staphylococcus aureus ATCC 29213 in broth media, but not against any of the other strains. The activity of teicoplanin, and less so that of vancomycin, was enhanced only against S. aureus strain ATCC 25923, but not against the other strains. It was concluded that susceptibility tests, excluding aminoglycoside antibiotics, of β-hemolytic streptococci, pneumococci, and H. influenzae and H. parainfluenzae should be incubated under 3% (candle jar or incubator) or 5% CO2 (incubator) so as to ensure optimal growth of capnephilic strains and thus avoid potentially misleading large inhibition zones or deceptively low minimal inhibitory concentrations.