One mechanism of granzyme B–independent cytotoxicity involving the Fas pathway. Allospecific day 5 MLR-derived CTLs (H-2^b anti–H-2^d) from granzyme B^+/+ (B^+/+), granzyme B^−/− (B^−/−), and granzyme B^−/− × gld/gld (B^−/− × g/g) spleens were used against allogeneic TA3 (H-2^d) lymphoma cells at a fixed E:T ratio of 10:1 in ⁵¹Cr release (A) and ¹²⁵IUdR release (B) assays. Note that granzyme B^−/− and granzyme B^−/− × gld/gld CTLs induce essentially normal levels of ⁵¹Cr release, whereas both effector populations are unable to mediate any ¹²⁵I-labeled DNA release at early time points. However, the defective ¹²⁵I-labeled DNA release is more severe in granzyme B^−/− × gld/gld cells than in CTLs deficient for granzyme B alone. Error bars show the range of values at each point. This experiment represents one of four with similar results.