An all oral treatment for cryptococcal meningitis is attractive, particularly where amphotericin B use is impractical. Both fluconazole and flucytosine are available in oral formulations and have activity against Cryptococcus neoformans. We conducted a prospective phase II dose escalation study employing doses of fluconazole ranging from 800 to 2000 mg daily for 10 weeks used alone or combined with flucytosine at 100 mg/kg per day for the first 4 weeks. We found that increasing doses of fluconazole were associated with an increase in survival and a decrease in the time to conversion of the cerebrospinal fluid from culture positive to culture negative. Addition of flucytosine to fluconazole improved outcomes in each dosing cohort. High doses of fluconazole alone or combined with flucytosine were well tolerated.