122 patients with hematologic malignancies underwent allogeneic marrow transplantation from HLA-matched sibling donors and received one of two forms of infection prophylaxis while granulocytopenic: 1) decontamination and laminar air flow isolation (LAF, 68 patients), and 2) LAF plus prophylactic systemic antibiotics (LAF+ PSA, 54 patients). Patients were evaluated for infection acquisition while in isolation. Septicemia occurred in 11 (16%) of the patients in the LAF group and in three (6%) patients in the LAF+ PSA group. Fourteen (21%) of the patients in the LAF group and four (7%) patients in the LAF+ PSA group had a major local infection. There was no difference in the incidence and severity of graft-versus-host disease or incidence and duration of fever. The addition of prophylactic intravenous broad-spectrum antibiotics for patients isolated in LAF rooms significantly decreased infection acquisition.