The in vitro activities of different daptomycin concentrations in combination with metronidazole (4 mg/l) or/and mezlocillin (8 mg/l) were investigated on mixed bacterial cultures involving gram-positive facultative cocci. Bacteroides fragilis group strains and Escherichia coli. When Streptococcus faecalis alone or together with E. coli was cultured with B. thetaiotaomicron the colony counts of the latter were 4 log units higher after incubation in the presence of daptomycin and metronidazole than when it was cultured alone. After the addition of mezlocillin, this effect disappeared and all 3 strains were killed. When the same antibiotic combinations were used in the presence of beta-lactamase producing Staphylococcus aureus, the activity of mezlocillin was decreased significantly. The colony counts of the co-cultured B. thetaiotaomicron and E. coli proved to be 2 log and 6 log higher, respectively, than those observed after they were cultured alone. The antimicrobial susceptibilities of the clinical isolates tested here in mixed cultures of up to 3 strains were modified significantly by interactions between the strains and the antibiotics used.