The in vitro activity of cefodizime (HR-221), a new cephalosporin antibiotic, was compared with the activities of selected antimicrobial agents against a broad spectrum of aerobic bacteria. Cefodizime concentrations of 2 micrograms/ml inhibited about 90% of Enterobacteriaceae studied. Serratia marcescens required 8 micrograms/ml to inhibit 90% of strains. Among gram-positive cocci, 50% of strains were inhibited by 2 micrograms/ml of cefodizime (including methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis, and penicillin-resistant Streptococcus pneumoniae). Pseudomonas aeruginosa was less susceptible to cefodizime. Cefotaxime, an antibiotic closely related to cefodizime structurally, was about fourfold more active.