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Neuropeptide Y, an abundant neurohormone present with catecholamines in the adrenal medulla, is a potent non-adrenergic vasoconstrictor and a vascular growth factor.To determine the mechanism of the release from, and possible role of neuropeptide Y in, pheochromocytomas, compared with those of catecholamines.Plasma and tumour levels of neuropeptide Y-immunoreactivity (by, radioimmunoassay) and of noradrenaline and adrenaline (by a radioenzymatic method) in 29 patients (19 women and 10 men, aged 22–68 years) were measured during surgical removal of the tumour, during α-adrenergic and β-adrenergic blockade. Arterial systemic blood samples were withdrawn before the ligation of the vessels supplying the tumour, during its surgical manipulations and after its removal, while haemodynamics was monitored.Plasma neuropeptide Y levels in 17 patients(58.6%, group I) significantly increased during manipulations of the pheochromocytoma and returned completely to normal after its removal. This response was independent of the plasma neuropeptide Y immunoreactivity manipulation and was correlated to increases in plasma noradrenaline (r = 0.638, P < 0.02) but not adrenaline levels. Manipulation-induced increases in plasma neuropeptide Y-immunoreactivity were associated with greater neuropeptide Y content in tumours (r = 0.508, P < 0.05) but neither plasma nor tumour levels of neuropeptide Y immunoreactivity were correlated to tumour mass. Plasma levels of neuropeptide Y immunoreactivity in the remaining 12 patients (41.4%, group II) remained unchanged throughout the experimental period, while levels of circulating catecholamine rose. In all, in spite of our attempt at complete adrenergic blockade, tumour manipulation elevated arterial blood pressure and these changes were significantly correlated to increases in levels of catecholamines in patients in both groups but also to plasma neuropeptide Y immunoreactivity in patients in group I.Pheochromocytomas exhibit different patterns of secretion. For about half of the patients either the secretion of neuropeptide Y is uncoupled from that of catecholamines or its secretion could be obscured by an increase in degradation of neuropeptide Y to inactive fragments undetectable by radioimmunoassay.