During a 2-year period, 15 of 110 patients (14%) admitted for intensive therapy of acute leukemia associated with prolonged deep granulocytopenia developed documented invasive aspergillosis (IA). Antemortem diagnosis was accomplished in 14, and 13 of 15 (87%) survived the infection. Because of the high success rate, we reviewed the courses of the 15 patients to assess factors associated with this favorable outcome. Eleven presented with pulmonary IA; early symptoms occurred at a mean 21.6 days of granulocytopenia (less than 100/muL) and included refractory fever in 14 and pulmonary signs or symptoms in 11. Primary necrotic chest wall lesions associated with Hickman catheters developed in four at a mean 11 days of granulocytopenia, followed by pulmonary involvement. All 15 patients had chest radiographs during granulocytopenia, with 14 (93%) demonstrating pulmonary infiltrates and/or nodules at a mean 20.6 days of aplasia. Nine patients had lung computerized tomography (CT) scans, revealing nodular infiltrates in one patient and a characteristic zone of low attenuation surrounding a mass-like infiltrate in seven other patients, which was found to be diagnostic of IA. Subsequent CT scans performed during and following bone marrow recovery showed progression to cavitation followed by either complete resolution or minimal pulmonary scarring. Eleven patients developed IA during empiric amphotericin B (Amp-B) therapy (0.5 mg/kg/d) for fever refractory to antibacterial antibiotics. Fourteen patients received high-dose Amp-B (1.0 to 1.5 mg/kg/d), which was started within a mean of 2.2 days of first clinical findings; 13 survived. Ten patients received 5-fluorocytosine in addition to high dose amp-B. Survival was similar regardless of presentation, as 91% with primary pulmonary IA and 75% presenting with chest wall lesions survived. All 13 surviving patients had complete granulocyte recovery at a mean 33.8 days. Nephrotoxicity (creatinine greater than 2.0 mg/dL) was observed in seven patients during therapy for IA, but was transient in all seven. We conclude IA can be successfully treated in the deeply granulocytopenic patient provided that it is recognized and treated early, and provided that antifungal therapy is aggressive and is continued until granulocyte recovery occurs.