The Streptococcus milleri group is associated with a spectrum of serious suppurative infections that have not been well defined. The purposes of this study were to ascertain the clinical significance of Streptococcus milleri bacteremia and to determine the epidemiological, clinical, and microbiological features of these infections compared to those caused by other viridans streptococci. All cases of streptococcal bacteremia observed in a Spanish hospital in the period from January 1988 to December 1994 were reviewed. Of 137 cases of Streptococcus milleri infection, 33 (24%) were documented cases of bacteremia. Twenty-four patients were men (mean age 57.8 +/- 17.4 years). The majority of infections were abdominal in origin (20/33), the most frequent diagnoses being cholangitis/cholecystitis (18%) and appendicitis (12%). The origin of infection could not be established in three cases. Nine cases of bacteremia (27%) were polymicrobial. Six patients (18%) had septic shock; in four the infection was polymicrobial, and in two the infection was of abdominal origin. Eighteen of the 33 patients (54%) required surgery. Five patients died. All 33 Streptococcus milleri isolates were susceptible to penicillin. Twenty-two cases of bacteremia caused by other viridans streptococci were observed during the same period. There were no statistically significant differences between the two groups in terms of age, sex, mortality, rate of polymicrobial infection, rate of nosocomial acquisition of bacteremia, or the occurrence of shock. An abdominal origin of infection was more frequent in Streptococcus milleri bacteremia (p = 0.0001); a cardiovascular origin was more frequent in the viridans group (p = 0.01), as was a diagnosis of endocarditis (p = 0.004). Four patients with viridans streptococci bacteremia required surgery versus 18 patients with Streptococcus milleri bacteremia (p = 0.01). Viridans streptococci were notably less susceptible to penicillin (89%), clindamycin (79%), and erythromycin (79%).