The use of empirical antibiotic combinations in the treatment of febrile neutropenic patients has decreased complication-related mortality in cancer patients. We have analyzed retrospectively 499 consecutive episodes of fever in 432 patients with acute lymphoblastic leukemia over a 5-year period. We have compared various antibiotic combinations used empirically in our study. Of the febrile episodes, 92% were neutropenic. The most common site of clinical documentation was the lung. The most common pathogen isolated in our setting was Pseudomonas aeruginosa (27.27%). The overall response rate to first-line empirical antibiotic combination was seen in 61.92%, the best results being with ceftazidime and amikacin combination (65.69%). A uniform antibiotic policy resulted in a decrease in mortality, with the number of deaths decreasing significantly in the 1989 to 1991 era (P = 0.00000003). The other contributing factors were an improvement in the supportive care with a reduction in length of hospital stay during induction. Our fungal isolates demonstrated 11 patients with documented fungal infection with a positive outcome in 8 patients.