The increase of sympathetic activity in heart failure is accompanied by reduced parasympathetic tone. The renin-angiotensin system (RAS) is often activated in heart failure. It not only has multiple interactions with the sympathetic nervous system but also may influence vagal tone directly via angiotensin II. Animal studies show a reduction of parasympathetic tone by a direct action of angiotensin II in the area postrema, where the blood-brain barrier is absent. It is possible that in addition to the sympathetic and renin-angiotensin systems the parasympathetic nervous system may also influence prognosis in heart failure. Therefore, baroreflex sensitivity (BS) as an index of vagal tone was examined in 35 patients with moderate-to-severe heart failure (NYHA II-III). Independent of the severity of heart failure, BS was lower the higher the plasma renin activity. At 56 months after initial examination, a comparison of the surviving patients (group 1, n = 20) with the patients who died or underwent heart transplantation (group 2, n = 15) did not reveal significant differences in the initial hemodynamic data. However, group 2 patients showed a tendency to higher initial plasma renin activity and a significantly lower BS (1.3 +/- 0.2 versus 2.2 +/- 0.3 ms/mm Hg; p < 0.05). It is concluded that in patients with heart failure a relation between the RAS and the parasympathetic nervous system is likely, as there is a significant negative relationship between BS and plasma renin activity. Among patients with similar degrees of heart failure, low vagal tone identifies patients with a poor prognosis.