The effectiveness of the fluoroquinolone ciprofloxacin is dependent on stromal drug concentrations which exceed the minimum inhibitory concentration90 (MIC90). The purpose of this study is to compare corneal tissue ciprofloxacin levels in patients exposed to three ciprofloxacin dosing regimens before undergoing penetrating keratoplasty. Thirty-one patients were assigned to one of three treatment groups. Group 1 followed a ciprofloxacin dosing regimen compatible with home use [two drops of 0.3% ciprofloxacin (Ciloxan; Alcon Laboratories, Fort Worth, TX, U.S.A.) every 4 h over a 24-h period]. Groups 2 and 3 followed a more tightly controlled dosing regimen designed for a health-care setting (two drops of Ciloxan applied by a trained professional every 15 min over a 4-h period). In groups 1 and 2, corneal epithelium was left intact, whereas in group 3 corneas were abraded. Corneal tissue samples were surgically obtained. Excised buttons were frozen and Ciloxan concentration determined by high-pressure liquid chromatography. Ciloxan corneal tissue concentrations (mean +/- SD) were 8.82 +/- 8.24 micrograms/g tissue in group 1, 166.20 +/- 336.94 micrograms/g tissue in group 2, and 938.30 +/- 1,081.51 micrograms/g tissue in group 3. Ciloxan penetration can be improved by administering the drug in a controlled setting at 15-min intervals over a 4-h period. Individual Ciloxan concentrations exceeded the MIC90 for most key ocular pathogens despite wide variability in all experimental groups.