Beta 2-microglobulin (beta 2m) -/- mice have often been used as a model to investigate host resistance to grafted tissues in the absence of CD8+ T cells. However, the realization that beta 2m -/- mice have a small pool of CD8+ T cells imply that these cells may take part in immune responses in vivo. To directly address the role of CD8+ T cell responses in beta 2m -/- mice, we introduced a CD8 null mutation into these mice. The beta 2m/CD8 -/- mice and the corresponding control mice were primed, and challenged with syngeneic tumour grafts. While beta 2m -/- mice readily cleared such tumour grafts, similar tumour grafts grew progressively in a dose dependent manner in the beta 2m/CD8 -/- mice. The present results imply that residual CD8+ T cells in beta 2m -/- mice may carry out significant biological functions, and suggest that studies using beta 2m -/- mice as a model for CD8+ T cell deficiency must be regarded with some caution.