Antibiotic therapy must be instituted promptly and on an empiric basis in neutropenic patients. We evaluated the efficacy of a combined antibiotic regimen of monobactam (aztreonam) and antipseudomonal penicillin (piperacillin) in treating neutropenic fever episodes in gynecologic-oncology patients receiving cisplatin-based chemotherapy. A retrospective analysis of response to this regimen was performed. The rationale of this combination is the lack of nephrotoxicity and ototoxicity in patients who are or were previously treated with other nephrotoxic/ototoxic agents like cisplatin. A total of 19 courses of this regimen was administered to 13 patients with neutropenic fever following a complete fever work-up. Aztreonam (l-2gr q8h) plus piperacillin (4gr q8h) were administered intravenously for 6-8 days. Blood cultures were positive in four febrile episodes, and urine cultures were positive in seven. Gram negative organisms accounted for all positive cultures. The cultured organism showed in-vitro sensitivity to at least one of the drugs in all positive isolates. Clinical response with defervescence was noted during therapy in 18/19 courses (94.7%). Although the two drugs share a common bactericidal mechanism they were found to be highly active in this subgroup of patients. A double blind prospective evaluation of this empiric combination is warranted.