A trial of the antifungal triazole fluconazole was conducted in cancer patients with presumed or proven mold infection. Groups of patients received fluconazole at four dosages (800, 1200, 1600, or 2000 mg/day). Adverse events, plasma levels, and clinical response were examined. Thirty-nine patients were enrolled. The 28 evaluable patients had presumed (13 patients) or proven (15) mold infection with Aspergillus (4) and Fusarium (3) species, Zygomycetes organisms (1), or nonspeciated mold (7). Adverse effects included elevated liver function test results (8 patients), nausea and vomiting (2), and erythema multiforme (1). Neurologic toxicity occurred in 3 patients receiving 2000 mg/day. Average steady-state peak plasma concentrations were 51.8, 74.4, and 91.8 mg/L for dosages 1200, 1600, and 2000 mg/day, respectively. Seven of 28 evaluable patients responded. Response did not appear to be related to dose. Fluconazole is well tolerated at total daily doses up to 1600 mg. The data suggest a linear plasma concentration-dose relationship. The activity of fluconazole in refractory mold infections seems to be limited.