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Two patients with cryptococcal meningitis were treated with the investigational triazole drug fluconazole (UK-49,858). Cerebrospinal fluid (CSF) levels of fluconazole were between 3.0 and 5.4 mg/l 2 h after an oral dose of 50 mg daily in the first patient and between 7.9 and 9.0 mg/l after an oral dose of 100 mg daily in the second patient. These levels were in the same range as plasma levels. The first patient, a 46-year-old renal transplant patient, was both clinically and microbiologically cured after 28 weeks of therapy (follow-up 14 months). In the second patient, a 15-year-old girl with chronic mucocutaneous candidiasis, fluconazole led to clinical cure of the meningitis, but failed to eradicate cryptococci from the CSF. These cases illustrate that fluconazole is useful for the treatment of cryptococcal meningitis, especially when prolonged treatment is indicated as in patients with immunodeficiencies.