The effects of neuropeptide Y (NPY) on cyclic AMP (cAMP) accumulation in slices of the dorsal midline area of the caudal part of the medulla oblongata containing the nucleus tractus solitarius (nTS) have been studied. Neuropeptide Y (30 and 300 nM) significantly reduced the [3H]cAMP accumulation induced by forskolin and phorboldibutyrate. Similar results were obtained after incubation with the alpha-adrenoceptor agonist clonidine (1 microM). These results indicate that stimulation of the NPY receptors and alpha-adrenoceptors in the nTS region may cause inhibition of the adenylate cyclase. Such a mechanism may at least partly underlie the centrally mediated hypotensive effects of the costored transmitters adrenaline and NPY.