99 patients with hematological malignancies underwent allogeneic marrow transplantation from HLA-identical sibling donors and were randomized to receive one of two forms of infection prophylaxis while granulocytopenic: (1) prophylactic systemic antibiotics in a conventional hospital room (PSA, 50 patients) or (2) decontamination, isolation in a laminar air flow room and the administration of prophylactic systemic antibiotics (LAF+PSA, 49 patients). Only 1 patient (3%) in the LAF+PSA group acquired septicemia while granulocytopenic compared to 11 (24%) patients in the PSA group (p<0.005). Three patients (6%) in the LAF+PSA group acquired major localized infections compared to 9 (18%) in the PSA group (p=0.06). There was no significant difference in days in hospital post transplant, days of granulocytopenia, days of fever, incidence of acute graft-versus-host disease, interstitial pneumonitis or overall survival. We conclude that the use of prophylactic systemic antibiotics added to decontamination and laminar air flow isolation of patients undergoing marrow transplantation significantly reduces the incidence of septicemia in the granulocytopenic period.