Nosocomial blood stream infections due to streptococci represent an increasingly important problem, particularly among neutropenic cancer patients. This problem is compounded by the emerging resistance to antimicrobial agents commonly used for empiric or prophylactic treatment of hospitalized patients. In this study, we examined the species distribution and antimicrobial susceptibility profile of 295 streptococcal nosocomial blood stream isolates from more than 30 U.S. medical centers (SCOPE National Surveillance Program). Streptococci accounted for 5.9% of all nosocomial blood stream isolates reported. The viridans group streptococci (VGS) were the most frequently isolated streptococci (50.8%), followed by the beta-haemolytic streptococci (31.9%) and pneumococci (13.2%). The beta-haemolytic streptococci were dominated by serogroup B strains (63%), followed by serogroups A and G. Of these organisms, 193 strains were referred for subsequent monitor susceptibility testing. Approximately 14% of S. pneumoniae, 9.2% of VGS, and 0% of beta-haemolytic streptococci were resistant to penicillin. Ceftriaxone was highly active against virtually all isolates (93-100% susceptible) except the VGS (77% susceptible). The rank order for activity of the four agents tested against the 193 isolates was vancomycin > ceftriaxone > penicillin > erythromycin. Importantly, 69% of the penicillin intermediate and resistant strains of VGS were also resistant to at least one additional antimicrobial (31% resistant to ceftriaxone, 51% resistant to erythromycin, 15% resistant to both ceftriaxone and erythromycin). The relatively poor activity of erythromycin against virtually all streptococci and the frequent association of macrolide resistance with penicillin resistance among the VGS suggests that both macrolides and beta-lactam agents might have limited value as prophylactic agents for dental procedures and in empiric or prophylactic use in neutropenic patients.