The Ifn-induced and dsrna-activated kinase (pkr) mediates the antiviral and antiproliferative effects of Ifn-α and Ifn-γ. Despite these findings, Pkr-/- mice have no overt immunological phenotype. Here we tested the role of Pkr in cellular immunity by determining the induction and elicitation of contact hypersensitivity in Pkr-/- mice, a model of T cell-mediated immunity. When compared with wild type, the magnitude of contact hypersensitivity responses in Pkr-/- mice were 2-fold higher and of extended duration. This was also observed when naive recipients of immune Cd8+ T cells from sensitized Pkr-/- and Cd4+ T cells from sensitized wild-type Pkr+/+ or Pkr-/- mice were challenged with hapten, indicating a regulatory defect intrinsic to the Cd8+ T cell population. Isolated lymph node T cells from Pkr-/- mice were hyperproliferative during Con A-mediated stimulation. These results implicate Pkr for the first time in the growth control of mature T lymphocytes and give insight into the negative regulation of Cd8+ T cell-mediated immune responses.