Circulating levels of extracellular matrix components were measured by radioimmunoassays and tested if they were useful for clinical staging in chronic heart failure. In 41 patients with dilated cardiomyopathy (33 idiopathic and 8 ischemic cases), the serum concentrations of procollagen type III aminoterminal peptide (PIIINP), type I collagen telopeptide (ICTP), and basement membrane laminin were significantly higher than in 30 healthy controls regardless of the underlying etiology. Patients with serum values of PIIINP, ICTP, and laminin > 7 micrograms/L, 7.6 micrograms/L, and 2.3 U/ml, respectively, were at higher relative risk for advanced clinical stage, poor hemodynamic condition, hyponatremia, heart transplantation, and death during follow-up than patients with low levels, with the exception that serum laminin > 2.3 U/ml was not significantly associated with hyponatremia and heart transplantation. Despite their interdependence on liver function, circulating levels of PIIINP and ICTP were independent predictors of mortality. In 17 of the 41 patients with cardiomyopathy whose explanted hearts were available for histologic evaluation, serum PIIINP, ICTP, and laminin significantly correlated with the myocardial area fractions of their tissue analogues (PIIINP vs myocardial collagen type III, r = 0.784, p = 0.0013; serum ICTP vs myocardial collagen type I, r = 0.603, p = 0.0527; and serum laminin vs myocardial laminin, r = 0.605, p = 0.0411). In conclusion, the increase in extracellular matrix turnover, which may partially be derived from fibrosis in the myocardium, can be measured in the serum of patients with dilated cardiomyopathy, and has an impact on risk stratification and prognosis.