The aim of this study was to compare the clinical and microbiological efficacy of netilmicin plus imipenem-cilastatin (Net + Imi) vs netilmicin plus ceftazidime (Net + Cef) as empiric antimicrobial therapy in bone marrow transplant (BMT) febrile neutropenic patients (pts). Sixty-six pts undergoing BMT for hematological malignancies and solid tumors were randomized to receive Net + Imi or Net + Cef as first-line antibiotic therapy. A lasting return of temperature to normal and complete disappearance of either clinical or cultural signs of infection without any modification of therapy was considered as improvement; the persistence of fever after 72 hours, the addition of a third antibiotic or a protocol change was considered as failure. Sixty-nine episodes were randomized during the course of the trial; bacteriological evidence of infection was obtained in 17 (25%) febrile episodes. Overall outcome based on clinical responses was as follows: 80% of pts on Net + Imi responded compared to 73% of those on Net + Cef. For microbiologically documented infections response rates were 70% in Net + Imi group and 43% in the Net + Cef group (p = ns). Neither septic death nor toxicity were observed. Both empiric regimens were shown to be effective; Net + Imi appeared to be more effective in microbiologically documented infections but there was no statistical significance. In conclusion, both Net + Imi and Net + Cef are active and safe as empirical treatment of febrile episodes in neutropenic BMT pts.