Both myocardial m-[I-123]iodobenzylguanidine (I-123-MIBG) uptake and plasma norepinephrine are markers of sympathetic activation in heart failure and have been shown to portend a poorer prognosis. However, these observations were noted before treatment with beta blockers became part of standard clinical practice. Fifty-eight patients with chronic heart failure (New York Heart Association functional class II and III, ejection fraction <35%; 53% ischaemic cardiomyopathy) were prospectively studied with a mean follow-up of 36 months. During the observational period, 17 patients (29.3%) had a predefined event (death and heart transplantation). All prognostic parameters were obtained before beta blocker therapy was initiated. In both uni- and multivariate analysis, the heart-mediastinum ratio of I-123-MIBG uptake did not correlate with cardiovascular mortality. In the multivariate Cox regression analysis, plasma norepinephrine, peak oxygen consumption, end-diastolic volume as measured by echocardiography and exercise performance during bicycling and walking had prognostic significance in patients with heart failure treated with beta blockers in addition to angiotensin-converting enzyme inhibitors. ((C) 2002 Lippincott Williams & Wilkins).