To understand the interaction between elastin and elastase, elastin from human aorta was incubated with human leukocyte elastase under conditions favoring proteolysis. Low molecular weight species were separated from the protein fraction by a small centrifuged gel filtration column. The only product of the elastin digest detected on acid polyacrylamide gel electrophoresis was a single band of slower cathodal mobility than human leukocyte elastase alone. This band cross-reacts with antibody to human elastase, indicating that the slow migrating band contains elastase. The putative human leukocyte elastase-elastin-derived peptide complex was treated with hydroxylamine to cleave any possible acyl-enzyme complexes and was then measured for amidolytic activity. Analysis of the amino acid composition of elastin-derived peptide indicates the presence of alanine, glycine, and richness in hydrophobic residues, suggesting that these residues are involved in elastase interaction(s). Incubation of the elastase-elastin-derived peptide with alpha 1-protease inhibitor causes dissociation of the complex and formation of an elastase-alpha 1-protease inhibitor complex. Our results suggest that, locally at the site of proteolysis, elastase activity may be regulated by elastin-derived peptide(s) during elastinolysis.