Aspartyl aldehyde, Ac‐Tyr‐Val‐Ala‐Asp‐H 1 (L–709,049), has been reported to be a potent, reversible inhibitor of interleukin‐1β converting enzyme (ICE) [Thornberry, N.A. et al. (1992) Nature (London)356, 768–774], In the context of our own work, we have developed a general synthetic approach to peptidic aspartyl aldehydes. Semicarbazone derivative, H‐Asp(Ot‐Bu)‐Sc 4, was identified as a stable, masked aspartyl aldehyde equivalent. We have used 4 to synthesize a series of mono‐, di‐ and tripeptide aldehydes, and multigram quantities of Ac‐Tyr‐Val‐Ala‐Asp‐H 1, Ac‐Tyr‐Val‐Lys‐Asp‐Sc 21 and Ac‐Tyr‐Val‐Lys‐Asp‐H 2. Biological evaluation of these aspartyl aldehydes and derivatives suggests that the tripeptide scaffold, Z‐Val‐Ala‐Asp, is a peptide scaffold that retains good potency and selectivity for ICE.