Bacterial infection is a common complication after allogeneic bone marrow transplantation. It is related to the toxic effects of the conditioning regimen on mucosal surfaces, to bone marrow aplasia and to the prolonged lymphopenia with immune deficiency that lasts for several weeks after bone marrow transplantation. We have performed a prospective randomized study comparing two methods of prophylaxis. Group I (OA) received a combination of ofloxacin 400 mg/day and amoxicillin 20 g/day; group II (VTC) received the oral nonabsorbable antibiotics vancomycin 450 mg/day, tobramycin 450 mg/day and colistin 4.5 · 10⁶ units daily, from day ––15 to 15 days after discharge from laminar air flow (LAF) rooms. All patients were nursed in LAF rooms with a strict isolation procedure and sterile water and food. They were evaluated daily for clinical symptoms, and bacterial culture samples were taken from the throat, stools and blood twice weekly. Forty-four patients were randomized, 22 entered in group I (OA) and 22 in group II (VTC). There were no differences between the two groups in age (mean 33 years, range 11–54), sex, diagnosis and mean duration of agranulocytosis (21.8 days, range 10–49). Seven patients were excluded because of the selection of a resistant bacteria, 5 were in group I (OA), and 2 were in group II (VTC). The mean duration of fever was 9.2 ± 7.1 days in group I (OA) and 13.7 ± 6.8 days in group II (VTC; p = 0.05). There were no significant differences between the two groups in graft-versus-host disease. During the period of follow-up, 3 patients died in group I (OA) of nonbacterial infections after cessation of the antibiotic prophylaxis. Five patients (all from group I) never received intravenous antibiotics; the mean duration was 28.7 ± 21.2 days in group I (OA) and 35.9 ± 13.1 days in group II (VTC). Failure to isolate bacteria from the feces occurred in 16/22 patients (72.7%) in group I (OA) and in 15/22 (68.2%) in group II (VTC). In group I, they were gram-positive streptococci and staphylococci while in group II they were gram-negative species. In the throat, no bacteria were isolated in 16/22 patients (72.7%) in group I and 11/22 patients (50%) in group II. Blood cultures were negative in 17/22 patients (77.3%) in group I and in 10/22 patients (45.5%) in group II. The main species found was Staphylococcus epidermidis in 4 cases in group I and in 19 cases in group II. There was no toxicity in either group, but the compliance seemed better in group I. In conclusion, this study shows that bacterial complications are a minor problem after allogeneic bone marrow transplantation. This is due to an improvement in strict isolation procedures and to decontamination. We show in this study that gut decontamination by oral nonabsorbable antibiotics is not sufficient and that the utilization of a combination of a new quinolone and amoxicillin provides a better protection against infection.