The study compared the pharmacokinetics and pharmacodynamics of ciprofloxacin and ofloxacin in 12 healthy male volunteers with normal renal function. Each volunteer received oral ciprofloxacin 500 mg, intravenous (iv) ciprofloxacin 400 mg, oral ofloxacin 400 mg, or iv ofloxacin 400 mg in a randomized, double-blind, crossover design with a one-week ‘washout’ period between doses. Mean peak serum concentrations were 4.48 and 5.44 mg/L for iv ciprofloxacin and ofloxacin, respectively. For the oral regimens, mean peak serum concentrations were 2.45 mg/L for ciprofloxacin and 4.44 mg/L for ofloxacin. Minimum bactericidal concentrations (MBC) and serum bactericidal activity (SBA) for each drug were measured against five strains of each of the following species: Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Pseudomonas aeruginosa, Acinetobacter anitratus, Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae, using the microdilution method of the National Committee for Clinical Laboratory Standards (NCCLS). Ciprofloxacin was more active in vitro than ofloxacin against the tested species of Enterobacteriaceae and P. aeruginosa, while ofloxacin was slightly more active against A. anitratus. MBCs for the two drugs were similar for H. influenzae and S. aureus. Oral and iv ciprofloxacin in the doses given resulted in nearly equivalent SBA. Similarly, oral and iv ofloxacin had nearly equivalent SBA. For the iv and oral regimens of both agents, peak SBA was ≥ 2 throughout the 12-hour test period against the Enterobacteriaceae and H. influenzae. At peak concentrations, both drugs had modest SBA against P. aeruginosa, A. anitratus, and S. aureus but little or no activity 8 and 12 h after dosing. Both drugs exhibited little or no SBA against S. pneumoniae. The peak SBA for ciprofloxacin was significantly greater than for ofloxacin against Enterobacteriaceae and P. aeruginosa. Trough SBA of the two drugs tended to be comparable. In this comparison of ciprofloxacin and ofloxacin, differences in in-vitro potency rather than serum pharmacokinetics determined in-vivo antibacterial activity measured by SBA.