Retinal toxicity resulting from the treatment of exogenous bacterial endophthalmitis with multiple antibiotics has increased the importance of evaluating the efficacy of new potent antibiotics for monotherapy. The retinal and corneal toxicity of ciprofloxacin hydrochloride, which is rapidly bactericidal against gram-positive and gram-negative bacteria, was evaluated in the rabbit eye. Retinal toxicity was dose-dependent in phakic and aphakic rabbit eyes as determined with electroretinography, light microscopy, and transmission electron microscopy. An intravitreal dose of greater than 100 micrograms also resulted in dose-dependent acute corneal toxicity in aphakic vitrectomized rabbit eyes. Results of instillation of ciprofloxacin directly into the anterior chamber of phakic rabbit eyes confirmed dose-dependent corneal toxicity. No retinal or corneal damage was observed in aphakic or phakic rabbit eyes after administration of an intravitreal dose of 100 micrograms. Results of electroretinography and light microscopy alone are insufficient to evaluate the retinal toxicity of antibiotics. Ultrasonic pachymetry is the best method of detecting probable associated corneal toxicity.