Ceftriaxone possesses potent activity, both in vitro and in vivo, against a broad range of bacteria. MIC50 and MIC90 geometric means were calculated using the results of broth and agar dilution assays performed worldwide. The MIC90 for ceftriaxone overall was 8 micrograms/ml or less for Enterobacteriaceae and 0.024 microgram/ml or less for Neisseria and Hemophilus species. Moderate activity was noted against Pseudomonas and Acinetobacter species (MIC50 12 to 28 micrograms/ml). Ceftriaxone was extremely active against nonenterococcal streptococci (MIC90 0.07 microgram/ml or less) and quite active against methicillin-susceptible Staphylococcus aureus (MIC90 5 micrograms/ml or less). Ceftriaxone generally was inactive against enterococci and methicillin-resistant staphylococci. Activity against anaerobes was good, except for many strains of Bacteroides fragilis and B. thetaiotaomicron (MIC greater than 64 micrograms/ml). Ceftriaxone exhibited excellent stability to beta-lactamases. The effect of medium and inoculum on in vitro testing was minimal. Excellent activity was demonstrated in vivo. Against Enterobacteriaceae, nonenterococcal streptococci, and H. influenzae, the PD50 in mice generally was less than 1 mg/kg. S. aureus strains responded moderately (mean PD50 6.5 mg/kg), whereas against most P. aeruginosa strains, PD50s ranged from 5 to greater than 250 mg/kg. The superior pharmacokinetic profile of ceftriaxone compared with that of other new cephalosporins was demonstrated by use of a prophylactic treatment schedule. The ability of ceftriaxone to penetrate the cerebrospinal fluid and provide excellent therapeutic coverage was confirmed in experimental meningitis models.