Due to its longer halflife, the N-terminal of ANF prohormone, ANF(1-98), has plasma concentrations that exceed those of ANF itself by a factor of 10 or more. It is also less prone to rapid changes secondary to hemodynamic alterations. To evaluate the prognostic significance of ANF(1-98) plasma levels in severe heart failure (NYHA IV), the peptide was measured by radioimmunoassay in plasma samples from patients randomized to additional treatment with enalapril (n = 78) or placebo (n = 61) (CONSENSUS study). In the placebo group there was a positive relation between mortality after 6 months and baseline ANF(1-98) level. Because of a reduced mortality, especially among patients with high ANF(1-98) levels, there was no such relation in the patients treated with enalapril. For both groups there was a positive relationship between increase in ANF(1-98) after 6 weeks of treatment and mortality, while a decrease signaled a favorable prognosis. It is concluded that the magnitude and changes of plasma ANF(1-98) provide information on prognosis and therapeutic effects with respect to mortality in patients with severe heart failure. Plasma ANF(1-98) may serve as a useful clinical biochemical parameter in the treatment of heart failure.