Currently, ica is considered to be the major operon responsible for staphylococcal biofilm. The effect of biofilm on susceptibility to staphylococcal infection of different implant materials in vivo is unclear. The interaction of ica-positive (wild-type (WT)) and ica-negative (ica(-)) Staphylococcus aureus and Staphylococcus epidermidis strains with titanium and both smooth and rough stainless steel surfaces was studied by scanning electron microscopy in vitro and in a mouse tissue cage model during 2 weeks following perioperative or postoperative inoculation in vivo. In vitro, WT S. epidermidis adhered equally and more strongly than did WT S. aureus to all materials. Both WT strains, but not ica(-) strains, showed multilayered biofilm. In vivo, 300 CFUs of WT and ica(-)S. aureus led, in all metal cages, to an infection with a high level of planktonic CFUs and only 0.89% adherent CFUs after 8 days. In contrast, 10(6) CFUs of the WT and ica(-) strains were required for postoperative infection with S. epidermidis. In all metal types, planktonic numbers of S. epidermidis dropped to <100 WT, and adherent CFUs were low in WT-infected cages and absent in ica(-)-infected cages after 14 days. Perioperative S. epidermidis inoculation resulted in slower clearance than postoperative inoculation, and in titanium cages adherent WT bacteria survived in higher numbers than ica(-) bacteria. In conclusion, the metal played a minor role in susceptibility to and persistence of staphylococcal infection; the presence of ica genes had a strong effect on biofilm in vitro and a weak effect in vivo; and S. epidermidis was more pathogenic when introduced during implantation than after implantation.