Monocyte/neutrophil elastase inhibitor (EI) is a protein of approximately 42,000 Mr with serpin-like functional properties. Remold-O'Donnell et al. (1992) cloned EI cDNA and identified 3 EI mRNA species of 1.5, 1.9, and 2.6 kb in monocyte-like cells and no hybridizing mRNA in lymphoblastoid cells lacking detectable EI enzymatic activity. The cDNA open reading frame encoded a 379-amino acid protein. Its sequence established EI as a member of the serpin superfamily. Sequence alignment indicated that the reactive center P1 residue is cys-344, consistent with abrogation of elastase inhibitory activity by iodoacetamide and making EI a naturally occurring cys-serpin. Other elastase inhibitors include alpha-1-antitrypsin (PI) and secretory leukocyte protease inhibitor (SLPI).