Acute blood volume expansion (AVE) is a potent stimulus for atrial natriuretic peptide (ANP) release. Since several central nervous structures are well known for their involvement in the regulation of fluid and electrolyte homeostasis and in the secretion of central ANP, we carried our experiments on 33 conscious Wistar rats in order to determine if the integrity of the supramammillary (SMA) hypothalamic area is essential for the peripheral ANP response to AVE. We performed stereotaxic electrolytic lesions of SMA in part of the animals. To obtain AVE we administered 2 mL saline/100 g b.m. for 2 minutes into v. jugularis through the chronically implanted venous catheters. Plasma ANP was assayed radioimmunologically. AVE significantly increased plasma ANP both in the intact animals and in the lesioned rats. This concluded that SMA is not involved in the regulation of peripheral ANP release during AVE.