The in vitro activity of cefixime and 9 other orally used antimicrobial agents against 545 selected clinical respiratory tract pathogens was tested using the plate-dilution method. or the strains tested, 144 were Haemophilus influenzae strains, 151 group A streptococci, 105 pneumococci and 145 Moraxella catarrhalis isolates. Ciprofloxacin was the most active drug, with a minimal inhibitory concentration (MIC) of < 0.06 mg/l for more than 87% of the isolates. With cefixime, a MIC of 0.06 mg/l inhibited 55% or the strains tested and a MIC of 1.0 mg/l inhibited all except one of the 545 strains. One pneumococcal strain was resistant to cefixime. Beta-lactamase producing H. influenzae and M. catarrhalis strains were clearly more susceptible to cefixime than to other oral cephalosporins (cephalexin, cefaclor, cefuroxime). However, penicillin, ampicillin and cefuroxime were more effective against beta-hemolytic streptococci and pneumococci than was cefixime. The new third generation cephalosporin, cefixime, showed markedly better in vitro activity against certain major respiratory tract pathogens than the other peroral antimicrobials commonly used against respiratory tract infections.