Elastin peptides obtained in vivo from the enzymatic degradation of elastic fibers are present in the circulating human blood. In order to verify the role that these peptides may have in the regulation of the vascular tone, the activity of several peptides identified in the elastolytic digest of human elastin and some of their structural homologues has been tested. Three of these peptides show a vasorelaxant activity in isolated rat aorta precontracted by phenylephrine. The activity observed is higher in the absence of the endothelium; in these conditions the IC50 for the peptides Val-Gly-Val-Ala-Pro-Gly, Val-Gly-Val-Pro-Gly and Val-Gly-Val-Hyp-Gly was 40 +/- 2, 73 +/- 2 and 10 +/- 1 ng/ml, respectively. They are active in the range of the pathological circulating concentration and their role could be important in the regulation of vascular tone during several elastin degradative diseases.