The incidence and clinical course of nosocomial septicemia with Streptococcus viridans was evaluated prospectively in 242 consecutive bone marrow transplant (BMT) recipients throughout their 15-213 days' (median 47) hospitalization, including 4-58 days (median 18) of neutropenia. Initial empiric therapy for febrile neutropenia consisted of mezlocillin, gentamicin and cefazolin; glycopeptide was excluded. S. viridans septicemia occurred in 23/209 (11%) subjects with underlying malignant disease, and only during neutropenia with concomitant mucositis: in 20 subjects (four with ampicillin-resistant strains), S. viridans septicemia occurred at onset of febrile neutropenia, 1-5 days (median 4.5) post-BMT. All survived with an uncomplicated clinical course. Thus, glycopeptide seems unnecessary in the initial empiric antibiotic regimen. The other three subjects demonstrated S. viridans septicemia (two with ampicillin-resistant strains) on day 11 post-BMT; two died. The major risk identified was cytosine arabinoside administration in the conditioning regimen (P < 0.01).