Activation‐induced natural killer (NK) cell death is very rapid compared to activation‐induced T or B cell death. Here we show that NK cell activation is accompanied by the leakage of granzymeB from intracellular granules into the cytoplasm. Evidence for granzyme B leakage includes the formation of granzyme B/serine proteinase inhibitor 9 (PI‐9) complexes that are detected by immunoprecipitation as well as colocalization of granzyme B and PI‐9 detected by immunocytochemistry. The pro‐apoptotic molecule Bid, a specific substrate for granzyme B, was cleaved within 2 min following CD2‐induced NK cell activation, suggesting that granzyme B triggers apoptosis by directing Bid to mitochondrial membranes. The granzyme B/PI‐9 protein ratio was found to mirror the percentage of CD2‐induced NK cell death, suggesting that an excess of leaked granzyme B over its inhibitor is a major determinant of cell death. We suggest that granzyme B leakage‐induced cell death is an important determinant of activation‐induced NK cell death and that this process may be important for the fate of NK cells which encounter malignant or virus‐infected cells.