Granzyme (grz) AB-/- H2b mice generate numerically normal cytotoxic T lymphocyte (CTL) responses to the prominent influenza A virus Db NP366 and Db PA224 epitopes and terminate the infectious process in the pneumonic lung with the same kinetics as the WT controls. Though grz B protein expression is fully compromised, there is only a partial effect on the level of CTL activity measured in a classical, short-term 51Cr release assay. Single-cell polymerase chain reaction (PCR) analysis of both highly activated effector and "resting" memory CD8+ T cells from influenza A virus-infected grzAB-/- mice showed a high prevalence of grzK mRNA+ expression in tetramer (tet)+ CTLs as was found in WT mice. However, a marked reduction in cytotoxicity present in the primary splenic CTLs of grzAB-/- mice correlated with decreased grzK expression, as measured by real-time PCR. This suggests that grzK plays an important role in CD8+ T-cell cytotoxicity both in the presence and absence of grzA and B.