gy T cells are thought to mediate immune responses at epithelial surfaces. We have quantified and characterized hepatic and peripheral blood gy T cells from 11 normal and 13 unresolved tumor-bearing human liver specimens. gy T cells are enriched in normal liver (6.6% of T cells) relative to matched blood (0.9%; P = 0.008). The majority express CD4CD8 phenotypes and many express CD56 and/or CD161. In vitro, hepatic gy T cells can be induced to kill tumor cell lines and release interferon-g, tumor necrosis factor-a, interleukin-2 and interleukin- 4. Analysis of Vgand Vy chain usage indicated that Vy3+ cells are expanded in normal livers (21.2% of gy T cells) compared to blood (0.5%; P = 0.001). Tumor-bearing livers had significant expansions and depletions of gy T cell subsets but normal cytolytic activity. This study identifies novel populations of liver T cells that may play a role in immunity against tumors.