Children with cancer who develop an episode of chemotherapy-induced febrile neutropenia usually are admitted to the hospital for intravenous empiric antibiotic therapy. In the current study, the authors examined the use of ciprofloxacin as outpatient management in selected patients with fever during an episode of neutropenia. Febrile neutropenic patients with a diagnosis of cancer were eligible for outpatient management with oral ciprofloxacin if they appeared well and demonstrated the following characteristics: age 1-21 years, malignancy in remission, absolute phagocyte count > 100/mm(3), > 7 days since the initiation of the last course of chemotherapy, and reliable parents. Eligible children received a single dose of ceftazidime and were observed for 2-23 hours. Patients were discharged receiving oral ciprofloxacin (20/mg/kg/day divided in 2 doses) until the patient was afebrile for 24 hours, had sterile blood cultures, and had evidence of bone marrow recovery. Patients were admitted if they appeared toxic, had positive blood cultures, or were febrile for >/= 5 days. Forty-five evaluable episodes occurred in 32 children. Forty of the 45 patients (89%) were treated successfully in the outpatient setting. The 95% lower confidence bound on the proportion of successful outcomes was 70%. Five children required hospitalization: 2 due to noncompliance, 1 to receive intravenous acyclovir for herpes zoster, and 2 (4%) whose blood cultures were positive for Streptococcus viridans and S. pneumoniae. All had uncomplicated hospitalizations. The current study demonstrates that very carefully selected, low risk patients with febrile neutropenia may be treated successfully without hospitalization using oral ciprofloxacin. Additional research is required to refine further the optimal criteria for the selection of appropriate patients for outpatient management.