The caspase inhibitor z-VAD improves survival in sepsis. A series of survival studies were performed in which ND4 mice underwent CLP and received antibiotics, as described in Methods. Next, mice received z-VAD or the diluent in which z-VAD was dissolved. The dose (mg/kg body weight) and time of administration of z-VAD are indicated in the upper left corner of each experiment. n = number of mice per group. (Exp. A) In this study, z-VAD was administered at the same time as CLP. Mice in the z-VAD group had improved survival; *, P < 0.003. (Exp. B) Mice received z-VAD (6 mg/kg) 1 hr after CLP. Mice treated with z-VAD had improved survival at 82–84 hr after CLP, compared with control mice; *, P < 0.04. (Exp. C) Mice received high-dose z-VAD (30 mg/kg) 1 hr after CLP. There was no difference in survival in the treated vs. untreated group. (Exp. D) Three separate studies were performed, and the results were combined. Mice received 20 mg/kg z-VAD or z-FA-FMK (z-Phe-Ala; a control noncaspase inhibitor that does have limited activity to block cathepsins) 1, 24, and 48 hr after CLP. A third group of mice (CONTROL) received the diluent for the z-VAD, i.e., DMSO in PBS (see Methods). Mice in the z-VAD-treated group had improved survival compared with both z-FA-FMK (P < 0.02) and control (P < 0.001).