The presence of Bim- and Bid-induced constant BH3 stress in the healthy liver causes hepatotoxicity with the use of anti-cancer agents that target anti-apoptotic Bcl-2 family proteins. The offspring from bim+/−bid−/− mating pairs were given an intraperitoneal injection of ABT-737 (100 mg/kg) or vehicle and were examined after 6 h. A, Western blot analysis of whole liver lysates for the expression of BimEL, Bid, Bcl-xL, Mcl-1, Bak, Bax, and β-actin. B and C, representative images of liver histology stained with hematoxylin-eosin and TUNEL (original magnifications, ×100 (large panels) and ×400 (insets)). D, TUNEL-positive cell ratio; n = 5–6 mice/group; *, p < 0.05 versus all. E, serum caspase-3/7 activity; more than 5 mice/group; *, p < 0.05 versus all. F, serum ALT levels; more than 5 mice/group; *, p < 0.05 versus all. Error bars, S.D. RLU, relative light units; I/U, international units.