Cardiotrophin-1 (CT-1) is a cytokine that has been implicated as a factor involved in myocardial remodelling. The objective of the present study was to establish the relationship between circulating levels of CT-1 and measures of left ventricular size and systolic function in patients with heart failure. We recruited 15 normal subjects [six male; median age 60 years (range 30-79 years)] and 15 patients [11 male; median age 66 years (range 43-84 years)] with a clinical diagnosis of heart failure and echocardiographic left ventricular systolic dysfunction (LVSD). Echocardiographic variables (left ventricular wall motion index, end-diastolic and -systolic volumes, stroke volume, fractional shortening) and plasma CT-1 levels were determined. In patients with LVSD [median wall motion index 0.6 (range 0.3-1.4)], CT-1 was elevated [median 110.4 fmol/ml (range 33-516 fmol/ml)] compared with controls [wall motion index 2 in all cases; median CT-1 level 34.2 fmol/ml (range 6.9-54.1 fmol/ml); P<0.0001]. Log CT-1 was correlated with log wall motion index (r=-0.76, P<0.0001), log left ventricular end-systolic volume (r=0.54, P<0.05), stroke volume (r=-0.60, P=0.007) and log fractional shortening (r=-0.70, P=0.001). In a multivariate model of the predictors of log wall motion index, the only significant predictor was log CT-1 (R(2)=56%, P=0.006). This is the first assessment of the relationship between plasma CT-1 levels and the degree of LVSD in humans, and demonstrates that CT-1 is elevated in heart failure in relation to the severity of LVSD.