In children undergoing anticancer chemotherapy, a granulocytopenic febrile episode is a life-threatening condition. Prompt initiation of empirical broad-spectrum antibiotics is essential to limit morbidity and mortality. To evaluate the cost-effectiveness of combination antibiotics consisting of a third generation cephalosporin and an aminoglycoside, a retrospective review of all febrile granulocytopenic patients admitted to our institution was conducted. Between June 1994 and August 1996, 183 febrile episodes in granulocytopenic children with cancer were empirically treated with ceftriaxone and amikacin in a single daily dose. 96/183 (52%) patients had absolute granulocyte count lower than 100/mm3 at the onset; 68 (37%) were affected by acute leukemia or lymphoma, 3 (1%) by chronic leukemia, 94 (51%) by solid tumors, and 21 (11%) patients underwent bone marrow transplantation. Ceftriaxone plus amikacin was effective in 135/183 (74%) patients with a median time to defervescence of 3 days (range 1-11). Economic evaluation (cost minimization analysis) was limited to the cost savings for nonreusable materials, and difference in direct drug costs in comparison with another combination regimen such as ceftazidime and amikacin. This analysis showed that compared to a 3 times daily regimen, administration of single daily doses of ceftriaxone would result in a net cost saving of US$ 11 (17,500 Italian liras) and US$ 65.6 (105,000 Italian liras) for a 1-day and a 6-day treatment period, respectively, for the treatment of a child of 30 kg body weight. Moreover, once daily therapy has the potential to lead to savings in the time of the nursing staff and may well contribute to an improved quality of life for febrile granulocytopenic children. For these reasons, in our department, ceftriaxone plus amikacin still remain the standard regimen for the empirical treatment of febrile granulocytopenic children with cancer.