Fluconazole dosages greater than 800 mg day-1 have been reported in about 900 patients treated for candidemia, oropharyngeal candidiasis and cryptococcal meningitis in HIV-infected patients, and for initial therapy of endemic mycoses. In patients with life-threatening infections caused by Candida spp., Cryptococcus neoformans and Coccidioides immitis, results of a limited number of dose-finding trials with non-neutropenic and HIV-infected patients show dose-dependent responses. These study results indicate that higher daily doses of fluconazole than are currently approved for these indications are well tolerated and tend to provide better clinical efficacy in selected patient populations. An excellent safety profile of dosages up to 2000 mg day-1 and linear predictable pharmacokinetics up to 1600 mg day-1 appear to justify further clinical investigations to better determine the optimum dosage and duration of treatment.