Between 1988 and 1991, 26 episodes of bacteremia due to viridans streptococci occurred in 25 neutropenic patients undergoing intensive chemotherapy for hematologic malignancies. Complications related to the bacteremia were observed in 10 episodes: unilateral pulmonary infiltrates (4), acute respiratory distress syndrome (ARDS) (4), hypotension (3), and endocarditis (2). All patients with ARDS had received high doses of cytosine arabinoside and had bacteremia due to Streptococcus mitis. Death occurred in three patients (12%) but was possibly related to bacteremia in only one case. Case patients who had received prophylaxis with quinolones were compared with matched control patients who received similar prophylaxis but who did not have bacteremia due to viridans streptococci. Multivariate analysis of predisposing factors showed that high doses of cytosine arabinoside (P = .01), the presence of mucositis (P = .02), and the absence of previous therapy with parenteral antibiotics (P = .01) were independent risk factors for the development of viridans streptococcal bacteremia. Of 259 patients who had received quinolone prophylaxis during the study period, 22 (8.5%) developed an episode of viridans streptococcal bacteremia as compared with three episodes (3.7%) in 82 patients who had received a quinolone and penicillin (P = .07). However, the latter three episodes were caused by strains with decreased susceptibility to penicillin, thus suggesting that resistance to penicillin might limit the use of this antibiotic as a prophylactic agent in the future.