Twenty-eight neutropenic (< 500 granulocytes/microliters) adults with microbiologically or histologically proven systemic mycosis were randomly assigned to receive either amphotericin B alone (0.5 mg/kg/day; n = 14) or amphotericin B (0.5 mg/kg/day) plus 5-flucytosine (150 mg/kg/day; n = 14) intravenously. Therapy was given for an average duration of 10 days in both groups, amounting to a total dose of amphotericin B of 338 mg and 308 mg, respectively. The mean duration of granulocytopenia was 18 days in the amphotericin B group and 20 days in the combination group. Only two patients treated with amphotericin B alone and three given the combination survived. Adverse events were similar in both groups with an elevation of the serum creatinine in six cases during the administration of amphotericin B alone and in seven cases treated with the combination. No other serious adverse events were encountered. Treatment with both regimens was disappointing partly because mycosis was too far advanced by the time therapy was begun and neutrophils were recovered in only half the patients.