We evaluated the efficacy of topical ciprofloxacin (3.0 mg/ml) in the treatment of experimental Pseudomonas aeruginosa keratitis in 60 rabbits. We compared ciprofloxacin treatment with double drug therapy consisting of tobramycin (13.6 mg/ml) plus polymyxin B (25,000 U/ml) or carbenicillin (6 mg/L). Two strains of P. aeruginosa were used. One was a strain well characterized for use in experimental Pseudomonas keratitis (ATCC organism 27853); the second was an organism from a patient with a Pseudomonas corneal ulcer. Rabbits were treated for 16 h, after which the corneas were excised, homogenized, and plated serially for residual colony-forming units. Both organisms responded significantly better to topical off-the-shelf ciprofloxacin than to therapy with two conventional antipseudomonal fortified antibiotic drugs (p =s 0.0001).