Objective: Hemorphin peptides exhibit biological activities that interfere with the endorphin system, the inflammatory response, and blood-pressure control. VV-hemorphin-7 and LVV-hemorphin-7 peptides exert a hypotensive effect, in particular, by inhibiting the renin-angiotensin system. Furthermore, levels of circulating hemorphin-7 peptides have been found to be decreased in diseases such as type 1 and type 2 diabetes. Design and Methods: Because type 2 diabetes and obesity share common features, such as insulin resistance, microinflammation, high glomerular-filtration rate (GFR), and cardiovascular risk, we evaluated serum VV-hemorphin-7 like immunoreactivity (VVH7-i.r.) levels, using an enzyme-linked immunosorbent assay method, on a group of 54 obese subjects without diabetes or hypertension, compared with a group of 33 healthy normal-weight subjects. Results: Circulating VVH7-i.r. levels were significantly decreased in the obese group compared with the control group (1.98 +/- 0.19 vs. 4.86 +/- 0.54 mu mol/l, respectively, P < 0.01), and a significant negative correlation between VVH7-i.r. and diastolic blood pressure (DBP) was found in obese patients (r = -0.35, P = 0.011). There was no significant correlation between VVH7-i.r. level and insulin resistance, metabolic syndrome, or GFR. Conclusions: The decreased serum hemorphin-7 found in obese subjects, as in diabetes, may contribute to the development of hypertension and to the cardiovascular risk associated with these metabolic diseases.