Ofloxacin, a new quinolone antibiotic with a broad spectrum of activity, is very effective against Pseudomonas aeruginosa in vitro. Its effectiveness was studied in a rabbit model of tobramycin-sensitive P. aeruginosa. Treatment groups received either vehicle, tobramycin 0.3%, or ofloxacin 0.3%. Twelve hours of treatment decreased the bacterial counts from a mean of 2.2 +/- 0.7 x 10(6) colony forming units (cfu) per cornea in the vehicle group to means of 513 +/- 670 and 435 +/- 524 cfu in the tobramycin and ofloxacin groups, respectively. This decrease in bacterial counts was statistically significant (p = 0.001 for tobramycin and ofloxacin each compared with control, p = 0.86 for tobramycin compared with ofloxacin). After seven days, all antibiotic-treated corneas were sterile and the epithelial defects healed at comparable rates. Aqueous humor drug levels were higher in infected eyes without an intact epithelium (p = 0.02); in eyes with intact epithelium, concentrations of ofloxacin were higher than were those of tobramycin (p = 0.002). In this animal model, ofloxacin proved to be an effective antibiotic with no evidence of toxicity.