OBJECTIVE A previous report suggested that high concentrations of ciprofloxacin in the anterior chamber may cause dose-dependent acute corneal decompensation. Therefore we evaluated the effect of varying concentrations of ciprofloxacin in the anterior chamber on the corneal endothelium and compared these effects with those of gentamicin and streptomycin. METHODS We assessed endothelial transport function by determining transendothelial electrical potential differences (TEPDs) of rabbit corneas. Our control solution was bicarbonate-buffered balanced saline with glucose (BSG), to which we added ciprofloxacin (50, 100, 125, and 150 microg/ml), gentamicin (1,000 and 2,000 microg/ml), and streptomycin (196, 437, and 696 microg/ml). RESULTS At high concentrations exceeding minimal inhibitory concentrations against 90% of common ocular isolates (MIC90), accelerated decay of TEPDs was seen with all three antibiotics. Adverse effects on TEPDs were noted at concentrations corresponding to >50 times MICs with ciprofloxacin and 40 x MICs with gentamicin, but only 2 times MICs with streptomycin. CONCLUSIONS Our study shows that concentrations of ciprofloxacin, gentamicin, and streptomycin below or equal to their MIC90 levels do not adversely affect endothelial transport function in a rabbit model.