This study was designed to determine the maximal safe drug concentration of intravitreal ciprofloxacin in phakic rabbit eyes. Twenty-two eyes of New Zealand pigmented rabbits received midvitreal ciprofloxacin of 100, 200, 400, 600 or 800 micrograms in BSS Plus, or BSS Plus only. Retinal toxicity was dose-dependent as determined with electroretinography, light microscopy, and transmission electron microscopy. At a dose of greater than 400 micrograms, disorganization of the outer segments was a main pathological finding in transmission electron microscopy. We evaluated retinal function by measuring the electroretinograms for a graded series of flash intensities and by fitting electroretinogram b-wave amplitudes to the Naka-Rushton equation. At a dose of greater than 600 micrograms, Rmax was significantly decreased and log K was significantly increased. N-value tended to decrease. A decrease of b-wave amplitudes caused by retinal toxicity could be detected very sensitively with lower luminance stimuli. Determination of retinal toxicity with lower luminance electroretinography revealed a significant decrease of b-wave amplitudes at a dose of greater than 400 micrograms. We concluded that a safe dose of intravitreal ciprofloxacin in phakic rabbit eyes was 200 micrograms in phakic eyes.