Several factors associated with bacterial biofilms were studied for their role in phenotypic resistance to antibiotics. These factors included bacterial slime extracted from biofilms, reduced growth rates of biofilm-embedded bacteria and high bacterial inocula. Antibiotic activity against suspended bacteria in the presence of these factors, either alone or combined, was compared with activity against adherent biofilms. All MICs, determined by standard susceptibility tests, were below the sensitivity breakpoints for Staphylococcus epidermidis strain V2. The addition of bacterial slime to suspended bacteria reduced the bactericidal activity of glycopeptides but had less or no effect on the activity of the other antibiotics tested. High bacterial inocula affected the activity of flucloxacillin and quinolones only moderately or not at all, though a more pronounced effect on glycopeptides was observed. In contrast, the bactericidal activity of most antibiotics was severely compromised when adherent bacterial biofilms were used as inocula. In conclusion, the presence of slime, slow growth rates and high bacterial counts may explain the poor activity of glycopeptides against biofilm-embedded organisms, but these factors, either alone or in combination, do not explain the lack of bactericidal activity of other drugs against biofilms. Thus, additional factors need to be identified.