The high number of gamma/delta-expressing T cells found in the epithelial lining layer suggests that they form a first line of defence against invading pathogens. To evaluate the role of gamma/delta T cell-receptor (TCR)-expressing cells in cutaneous infection caused by Staphylococcus aureus, mice lacking gamma/delta-expressing T cells (TCRdelta-/-) were inoculated intradermally with S. aureus, and compared with S. aureus-infected congeneic TCRdelta+/- control mice. The number of bacteria recovered from the skin of TCRdelta-/- mice was significantly higher (P = 0.0071) at early time-points after inoculation compared to the number of bacteria isolated from infected TCRdelta+/- congeneic controls. Nevertheless, inflammatory responses measured as serum IL-6 levels, were significantly lower in TCRdelta-/- mice than in the control group. A possible explanation for this discrepancy was the observation of significantly decreased overall numbers of infiltrating cutaneous T lymphocytes, which are important producers of IL-6. These results support the notion that the gamma/delta-expressing T cells that reside at the epithelial lining layer of the skin is of importance for early containment of the bacteria, thereby limiting their replication and spread.