The structured lymphoid tissues are considered the only inductive sites where primary T-cell immune responses occur. The naïve T cells in structured lymphoid tissues, once being primed by antigen-bearing dendritic cells, differentiate into memory T cells and traffic back to the mucosal sites through the bloodstream. Contrary to this belief, here we show that the vaginal type-II mucosa itself, despite the lack of structured lymphoid tissues, can act as an inductive site during primary CD8(+) T-cell immune responses. We provide evidence that the vaginal mucosa supports both the local immune priming of naïve CD8(+) T cells and the local expansion of antigen-specific CD8(+) T cells, thereby demonstrating a different paradigm for primary mucosal T-cell immune induction.