To evaluate the current role of ceftazidime plus amikacin as empiric therapy in the management of fever in neutropenic patients with acute leukemia, we examined 172 febrile episodes in 106 patients enrolled during 1996-98. The overall success rate (survival of neutropenia, both with and without protocol modification) was 90%: 39% without modification and 51% with modification. We documented a significant difference in documented infections (DI) and fever of undetermined origin (FUO): success without modification was lower in DI and higher in FUO. Failure (death due to documented or presumed infection) was recorded in 10% of all episodes. Episodes with severe neutropenia were treated in 48% of cases without modification and in 41% with modification. No significant difference was observed in the status of underlying disease. 33% of gram-negative bacteria responsible for bloodstream infections were resistant to ceftazidime, of which 21% were multiresistant strains. We conclude that initial chemotherapy with ceftazidime plus amikacin remains a reasonable option for treating febrile and prolonged neutropenia, although patients with DI are likely to require additional or modified treatment. The emergence of resistant strains is an increasingly important issue.