Interleukin-1 beta converting enzyme (ICE) processes an inactive precursor to the proinflammatory cytokine, Interleukln-1 beta, and may regulate programmed cell death in neuronal cells. The high-resolution structure of human ICE In complex with an inhibitor has been determined by X-ray diffraction. The structure confirms the relationship between human ICE and cell-death proteins in other organisms. The active site spans both the 10 and 20K subunits, which associate to form a tetramer, suggesting a mechanism for ICE autoactivation.