The serum bactericidal activities of ceftizoxime and ceftriaxone against organisms commonly implicated in community-acquired and nosocomial pneumonias were studied. Ceftizoxime 1 g (as the sodium salt) every 12 hours for two doses and ceftriaxone 1 g (as the sodium salt) every 24 hours for two doses were administered to 20 healthy volunteers in a crossover fashion. Blood samples were drawn immediately before and 2,4,6,8,10, and 12 hours after the second ceftizoxime dose and immediately before and 8,12,16,18,20, and 24 hours after the second ceftriaxone dose. Serum drug concentrations were determined by validated high-performance liquid chromatography. Serum bactericidal titers were determined in duplicate for each serum sample against four clinical isolates of each of the following organisms: Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, and Serratia marcescens. The median duration of serum bactericidal activity during the dosage interval was significantly different between antimicrobial regimens only for S. pneumoniae (92% of the dosage interval for ceftizoxime, versus 100% for ceftriaxone). This difference does not appear to be clinically important since ceftizoxime provides adequate serum bactericidal activity for more than 50% of the dosage interval and its effectiveness against pneumococcal pneumonia has been supported in clinical trials. The ceftriaxone and ceftizoxime regimens did not differ significantly in their duration of serum bactericidal activity against six of the seven organisms tested.