In the present investigations, gammadelta T cells were isolated from the peripheral blood of oral cancer patients and analyzed for their immunophenotype and cytotoxic potential. Flow-cytometric analysis revealed a dominant population expressing Vgamma9 and Vdelta2 T-cell receptors. In a 4-hr 51Cr-release assay, activated gammadelta T cells showed specific cytotoxicity against Daudi Burkitt's lymphoma cells and fresh oral tumor cells. Cold target competition assays demonstrated that gammadelta T cells recognize a common ligand on Daudi and oral tumor cells. Expression of heat shock protein 60 (hsp60) molecules was detected on the surface of Daudi as well as oral tumor cells by flow cytometry and immunoprecipitation of surface biotinylated cells by anti-hsp60 monoclonal antibody (MAb). Such MAbs brought about a significant inhibition of cytotoxicity of gammadelta T cells against Daudi and oral tumor cells. The results suggest that gammadelta T cells isolated from the peripheral blood of oral cancer patients have the ability to lyse oral tumor cells. The lysis of oral tumor cells occurs via recognition of hsp60 on the surface of oral tumor cells.