Abnormalities of the autonomic nervous system are known to be of prognostic significance in chronic heart failure (CHF). The prognostic value of positron emission tomography (PET) imaging of cardiac autonomic innervation in CHF has not been explored previously. We retrospectively studied the survival data of 46 NYHA class II-III CHF patients (mean LVEF 35% +/- 8%) who had undergone carbon-11 hydroxyephedrine (11C-HED) studies at the Turku PET Centre between August 1992 and March 1996. The origin of CHF was dilated cardiomyopathy in 13 of the 46 patients and coronary artery disease with at least one prior myocardial infarction in the remaining 33. Data on causes of death and heart transplantation were collected, and the statistically significant predictors of prognosis were analysed using Cox's proportional hazards regression. During the mean follow-up period of 55 +/- 19 months, 11 deaths occurred and two patients underwent heart transplantation successfully. Eleven end-points were classified as cardiac (nine sudden cardiac deaths and two deaths due to progressive heart failure) and two as non-cardiac. When divided into two groups based on the median of 11C-HED retention (mean 0.184 +/- 0.061, median 0.183), eight end-points (death or cardiac transplantation) were reached in the group with 11C-HED retention below the median and three in the group with 11C-HED retention above the median (P < 0.02). In proportional hazards regression analysis, only peak oxygen uptake (peak VO2), left ventricular end-diastolic volume and HED retention were found to be statistically significant. It is concluded that 11C-HED PET provides independent prognostic information in patients with CHF.