Gammadelta T cells recognize unprocessed or non-peptide Ags, respond rapidly to infection, and localize to mucosal surfaces. We have hypothesized that the innate functions of gammadelta T cells may be more similar to those of cells of the myeloid lineage than to other T cells. To begin to test this assumption, we have analyzed the direct response of cultured human and peripheral blood bovine gammadelta T cells to pathogen associated molecular patterns (PAMPs) in the absence of APCs using microarray, real-time RT-PCR, proteome array, and chemotaxis assays. Our results indicate that purified gammadelta T cells respond directly to PAMPs by increasing expression of chemokine and activation-related genes. The response was distinct from that to known gammadelta T cell Ags and different from the response of myeloid cells to PAMPs. In addition, we have analyzed the expression of a variety of PAMP receptors in gammadelta T cells. Freshly purified bovine gammadelta T cells responded more robustly to PAMPs than did cultured human cells and expressed measurable mRNA encoding a variety of PAMP receptors. Our results suggest that rapid response to PAMPs through the expression of PAMP receptors may be another innate role of gammadelta T cells.