We conducted a non-randomized, prospective study comparing the efficacy of tosulfloxacin with that of norfloxacin in preventing bacterial infection during chemotherapy-induced neutropenic episode. Fifty-one patients with hematological malignancies were included, and a total of 108 episodes of neutropenia were studied. There was no significant difference between the two groups in the incidence of fever, in the time-to-event analysis of febrile episodes nor in the incidence of gram-positive bacteremia despite the broader spectrum of tosulfloxacin. The incidence of gram-negative bacteremia was lower in patients treated with the quinolones as a prophylactic than in the historical controls given polymyxin B. Especially the incidence of bacteremia due to Pseudomonas aeruginosa was significantly less when tosulfloxacin was used. A possible synergistic effect of sulfamethoxazole-trimethoprim in preventing the febrile episode was also observed.