We evaluated the efficacy of piperacillin-pefloxacin as a non-nephrotoxic antibiotic combination in febrile neutropenic cancer patients treated with nephrotoxic chemotherapy. 40 patients: 34 with solid tumours and 6 with non-Hodgkin lymphoma, were treated during 55 episodes with: piperacillin 4 g intravenously every 8 h and pefloxacin 400 mg intravenously every 12 h. If the patient remained febrile after 72 h, 1 g vancomycin intravenously was added every 12 h. The mean duration of neutropenia was 7 days (range 3-13). Infection was microbiologically documented in 13 episodes (8 gram-positive cocci and 7 gram-negative bacilli). Temperature became normal in 38 patients with piperacillin-pefloxacin and 12 further episodes were resolved by the addition of vancomycin. 2 patients had an early change of antibiotics because of clinical deterioration, there were 2 protocol violations and 1 patient's temperature became normal after the addition of amphotericin. Neither septic death nor toxicity were observed. We conclude that this empirical treatment is active and safe and warrants further comparative trials.