Heart failure is an important reason for morbidity and mortality in patients with carcinoid. Carcinoid heart disease is caused by increased levels of circulating serotonin. Because carcinoids also produce catecholamines, we evaluated cardiovascular manifestations of autonomic dysfunction in patients with a carcinoid syndrome.Twenty patients with a midgut carcinoid, who had a carcinoid syndrome with a median duration of 72 months, and markedly elevated urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion were studied.Ten patients had no symptoms of heart failure, i.e. New York Heart Association (NYHA) functional class I, 6 had class II, and 4 class III heart failure. Transthoracic echocardiography (TTE) showed right-sided valvular abnormalities in 13 of 19 evaluable patients (mild n=8, severe n=5). Fourteen of the 20 patients (70%) had an elevated concentration of plasma N-terminal atrial natriuretic peptide (N-ANP), which correlated with NYHA class, TTE abnormalities, and increased urinary metanephrine excretion. Heart rate variability (HRV) parameters, in particular those associated with increased sympathetic activity (low frequency power, p=0.002 versus healthy individuals), were impaired but were independent of NYHA class and TTE findings and correlated with urinary metanephrine excretion (r=-0.49, p<0.05).In these 20 carcinoid patients with substantial secretory activity of the tumour, overt cardiac morphological changes were present in a minority of patients. However, N-ANP values and HRV profile were markedly abnormal, and related to enhanced urinary excretion of catecholamine and metabolites, suggesting autonomic derangement. These abnormalities possibly herald the development of more severe cardiac dysfunction and may be indicative of the need for preventive drug treatment.