Caspase 4 (also known as caspase 11) is a critical upstream regulator in the caspase cascade with an important dual role in regulating both inflammatory response and apoptosis. Splenocytes harvested from homozygous mice both before and after treatment with LPS show an absence of casp-11 protein isoforms. While casp-11-defeciency has no effect upon the expression of Interleukin-1b(IL-1?)-converting enzyme (ICE or caspase-1) precursor/immature proteins (pro-ICE), ICE activation (via proteolytic cleavage of pro-ICE) is defective. As such, homozygotes are severely defective in IL-1? maturation and secretion after LPS stimulation, and are resistant to LPS-induced septic shock. Homozygous mice are also resistant to the inflammatory/apoptotic Parkinson's disease-like pathology that results following acute MPTP neurotoxin administration. Homozygotes are viable and fertile. These mice may be useful in studying cell migration, cytokine maturation/secretion, and apoptosis during inflammatory responses, as well as actin dynamics (actin depolymerization) or neurotoxicity. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background.