• The ocular penetration and distribution of oral fluconazole was studied in Dutch-belted rabbits. Measured by high-pressure liquid chromatography, fluconazole readily penetrated all ocular tissues and fluids. No difference was observed between the levels obtained in phakic and aphakic eyes. Four hours after a single oral dose of 20 mg/kg, the mean levels and SEs were as follows: cornea, 13.3 ± 1.4μg/g; aqueous, 7.4 ± 0.3 mg/L; vitreous, 9.8 ± 0.9 mg/L; and choroid/retina, 5.2 ± 0.4 μg/g. These levels were approximately twice those obtained with a 10-mg/kg dose. The corneal concentrations correlated highly with serum levels (r =.89). A steady accumulation in both normal corneas and corneas infected with Candida albicans was noted when 17.5 mg/kg of fluconazole was administered twice daily over a 5-day period. Drug levels did not increase in the cornea when fluconazole was administered as a single daily dose of 35 mg/kg. In view of its excellent ocular pharmacokinetic profile, fluconazole merits further attention as an orally administered agent for ocular fungal infections.