Prophylactic systemic antibiotic therapy with ceftriaxone alone was tested in aplastic patients receiving total gut decontamination and treated in a protected environment. Only patients who were afebrile when their polymorphonuclear (PMN) count fell below 500/cumm were admitted to the study. Seventy-eight episodes of therapeutic aplasia (consecutive to allogeneic or autologous bone marrow transplant conditioning regimens or to high dose chemotherapy) form the basis of this report. The median duration of aplasia was 19 days (range 11-93 days). Twenty patients received, during 22 episodes of aplasia, one single injection of ceftriaxone per day as soon as their PMN count was below 500/mm3. In 13 cases (59%) the patients remained afebrile until the end of aplasia, and no bacteriemia was detected. The second part of the study was randomized between group A (prophylactic ceftriaxone: 29 cases) and group B (no prophylactic ceftriaxone: 27 cases). Patients in group A had significantly more episodes of afebrile aplasia (34.5% vs 4%) and less bacteriemias (10% vs 48%) than those in group B. Also fever developed later in group A (mean: 12.5 vs 6 days). No death was recorded throughout the study. Thus, in a protected environment prophylactic systemic antibiotic therapy could still lessen the risk of bacterial infection. Using one single antibiotic seemed to reduce the side-effects and cost of the prophylactic treatment.