A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation was conducted to ascertain the incidence and outcome of Streptococcus viridans bacteremia as well as to determine the role of prophylactic ampicillin therapy in the peri-transplant setting. Viridans streptococci were isolated from the blood of 35 individuals at a median of 6 days (range 2-8 days) following stem cell infusion. The most common isolates were S. sanguis and S. mitis. All patients received ciprofloxacin orally during the peri-transplant period. Additionally, 79 patients received oral ampicillin prophylactically against gram-positive cocci. Although none of the patients suffered a fatal outcome, three individuals developed respiratory compromise requiring mechanical ventilation. Female sex proved to be the only independent risk factor for viridans streptococcal bacteremia (P=0.04). The shorter duration of neutropenia observed after stem cell transplantation did not impact on the incidence of S. viridans infections. Moreover, the prophylactic use of ampicillin failed to decrease the incidence of viridans sepsis and selected out organisms that were resistant to beta-lactam antibiotics.