An incidence of up to 30% of systemic fungal infections at autopsy, and difficulties in diagnosing systemic mycosis antemortem, have led to the empiric use of amphotericin B in patients with hematological malignancies. Routine empiric anti-fungal treatment was initiated at our institution in 1982. Amphotericin B and initially for 3 days flucytosine was given to granulocytopenic patients with unremitting (after 48-72 h) or recurrent fever during antibiotic treatment, or with newly detected pulmonary infiltrates, sinusitis, and skin and retinal lesions suggestive of fungal infection. With this approach the rate of systemic fungal infections decreased from 10% to 4% (p less than 0.02). The reduction was most prominent in patients with acute myelogenous leukemia, where fungal infections decreased from 16% to 4% (p less than 0.025).