In the cardiovascular system, parathyroid hormone-related peptide (PTHrP) is expressed in various cells such as cardiac vascular smooth muscle cells, coronary endothelial cells and cardiomyocytes and acts as an autocrine/paracrine substance. We compared PTHrP levels in 35 consecutive patients with severe CHF (33 male, mean age 66.2 +/- 8.9 years) with 26 normal controls (24 male, mean age 63.1 +/- 8.6 years). PTHrP levels were reduced in severe CHF patients (11.10 +/- 1.37 fmol/ml) compared with the controls (20.62 +/- 3.30 fmol/ml, p = 0.005). PTHrP values decreased as a function of New York Heart Association classification. These results suggest that PTHrP levels decrease in proportion to the severity of heart failure and could potentially be used to monitor progression of disease non-invasively.