Endothelin-1[1-31] is a recently discovered member of the endothelin family with vasoactive properties in several animal models and in man in vivo. It is generated from big endothelin-1 by human mast cell chymase and may be a novel intermediary peptide in the production of endothelin-1[1-21]. Given that both big endothelin-1[1-38] and chymase activity are increased in chronic heart failure, the aim of this study was to determine whether plasma endothelin-1[1-31] concentrations are elevated in patients with chronic heart failure. Plasma endothelin-1[1-31] concentrations were measured by enzyme-linked immunosorbent assay in nine patients with chronic heart failure, and nine age- and sex-matched control subjects. Consistent with previous studies, plasma concentrations of big endothelin-1[1-38] were elevated in patients compared with controls (17.1 +/- 4.4 pg/mL vs 8.9 +/- 3.4 pg/mL, P = 0.002), although there were no differences in plasma endothelin-1[1-21] (3.3 +/- 0.4 pg/mL vs 3.4 +/- 0.7 pg/mL, P = 0.7) or endothelin-1[1-31] (both 1.1 +/- 0.1 pg/mL, P = 0.2) concentrations. We have demonstrated that patients with chronic heart failure have normal plasma endothelin-1[1-31] concentrations. This suggests that, in contrast to big endothelin-1[1-38], plasma endothelin-1[1-31] is unlikely to be a useful prognostic marker in patients with chronic heart failure.