The in vitro activity of ceftriaxone against 437 clinical isolates of gram-negative bacilli was determined. Ceftriaxone was found to have high in vitro activity against Enterobacteriaceae, with the exception of Enterobacter cloacae. Ceftriaxone was only minimally active against Pseudomonas aeruginosa and Acinetobacter calcoaceticus. We evaluated the clinical efficacy and toxicity of ceftriaxone in 55 adult patients. Bacterial infection was confirmed by the isolation of etiological bacteria in 30 patients. Infectious disorders treated included 10 pneumonias, 13 urinary tract infections, and 7 soft tissue or bone infections. Pathogens identified were 25 isolates of gram-negative bacilli, 5 isolates of Staphylococcus aureus, 5 isolates of pneumococci, and 4 isolates of other streptococci. The overall efficacy of ceftriaxone was excellent. The clinical cure rate was 93%, and the bacteriological cure rate was 93%. A total of 30 adverse reactions were noted in 22 of 55 patients receiving ceftriaxone, but only one necessitated discontinuation of treatment. Adverse effects frequently noted were elevated hepatic enzymes (16%), thrombocytosis (16%), and eosinophilia (8%). Ceftriaxone is an effective and well-tolerated antimicrobial agent that appears promising for the treatment of serious gram-negative bacillary infections.