The neuronal apoptosis inhibitory protein (NAIP) is a member of a novel family of inhibitor of apoptosis (IAP) proteins. The IAP genes are highly conserved from baculovirus to metazoans and suppress apoptosis induced by a variety of triggers both in vitro and in vivo. Here we describe the generation and characterization of mice with the targeted deletion of NAIP1. We demonstrate that the NAIP1-deleted mice develop normally. However, the survival of pyramidal neurons in the hippocampus after kainic acid-induced limbic seizures is greatly reduced in the NAIP1 knock-out animals. Thus, although NAIP1 is not necessary for normal development of murine central nervous system, the endogenous NAIP1 is required for neuronal survival in pathological conditions.