The purpose of this study was to determine the aqueous levels and pharmacokinetics of topical fluconazole 0.2 % upon single and multiple drop applications. Forty-nine patients undergoing cataract surgery were given topical fluconazole 0.2 %. They either received single drop or a loading dose of 1 drop per 5 min for 20 min. Aqueous samples were obtained during surgery 5, 15, 30, 45 and 60 min after the last drop. The samples were analysed by high-pressure liquid chromatography to determine aqueous concentrations. After single and loading dose applications peak aqueous levels were achieved at 15 min(3.35 +/- 0.64 and 7.13 +/- 0.79 mug ml(-1), respectively). Both had a steady decrease in concentration at 30, 45 and 60 min down to 4.06 +/- 0.37 mug ml(-1) with loading dose and undetectable levels with single dose application. Comparing the concentrations with the minimum inhibitory concentrations (MIC) of yeasts determined by the National Committee for Clinical Laboratory Standards showed that concentrations achieved with single dose applications were higher than MICs of Candida albicans and Candida parapsilosis and concentrations achieved after loading dose applications were higher than MICs of C. parapsilosis, C. albicans and Candida tropicalis. We concluded that topical fluconazole 0.2 % penetrates into the aqueous humor in concentrations that satisfy MICs of most of the Candida strains. It can be a good alternative to Amphotericin B for treatment of Candida keratitis. (C) 2001 Academic Press.