Interleukin-1 beta-converting enzyme (ICE), involved in the maturation process of interleukin-1 beta (IL-1 beta, is a homologue of ced-3, a protease required for programmed cell death in Caenorhabditis elegans. Over-expression of ICE induces programmed cell death in certain mammalian cell types, whereas in neurones of the central nervous system such a role has yet to be established. We show that ICE mRNA expression is increased 4-fold in the cerebellum of homozygous staggerer mice, where IL-1 beta mRNA is overexpressed and programmed neuronal cell death occurs. Intraperitoneal injection of endotoxin (LPS) induced a strong phasic increase in IL mRNA levels in the cerebellum, whereas the ICE mRNA level increased only moderately. Involvement of ICE in neuronal cell death in the cerebellum of staggerer mice is suspected.