Although IL-17-producing CD8(+) T cells (Tc17 cells) have recently been identified, the detailed information about these cells still remains unclear. In this article we describe a study investigating the phenotype and differentiation of human Tc17 cells. Human Tc17 cells were detected in a minor population of CD8(+) T cells and were predominantly found in CD27(-/+)CD28(+)CD45RA(-) memory subsets. They also expressed CCR6 and a high level of CCR5. Though most Tc17 cells produced IFN-gamma, a small part of the Tc17 cell population was IFN-gamma negative in some individuals. Analysis of the in vitro induction of Tc17 cells showed that these cells were induced from the CD27(+)CD28(+)CD45RA(+) naive subset and that they expressed the CD27(-)CD28(+)CD45RA(-) and CCR6(+) phenotype. These results together indicate that Tc17 cells have a unique phenotype and suggest that they differentiate from the same precursors that differentiate into IFN-gamma-producing CD8(+) T cells.