1 Intracellular recordings were made from neurones of the submucous plexus and from submucosal arteriolar smooth muscle of guinea-pig ileum for the purpose of examining the the actions of 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT). 2 8-OH-DPAT (10 nM-20 microM) had no direct presynaptic or postsynaptic actions on submucous plexus neurones. 3 Membrane hyperpolarizations induced in neurones by noradrenaline or UK 14304 were competitively antagonized by 8-OH-DPAT. For dose-ratios up to 40, Schild plots were linear with slopes not significantly different from unity; pA2 values for the 8-OH-DPAT antagonism of postsynaptic alpha 2-adrenoceptors were 6.9-7.2. 4 The inhibitory synaptic potential, which is due to activation of alpha 2-adrenoceptors located on submucous plexus neurones, was selectively inhibited by 8-OH-DPAT; the IC50 value for inhibition of the inhibitory synaptic potential was 250 nM. 5 Neuronal hyperpolarizations mediated through activation of delta-opioid receptors or somatostatin receptors were unaffected by 8-OH-DPAT (0.1-1 microM). 6 The ability of noradrenaline and UK 14304 to inhibit the release of acetylcholine at synapses in the submucous plexus, and to inhibit the release of the transmitter which mediates the excitatory junction potential in the submucosal arteriolar smooth muscle, was also blocked by 8-OH-DPAT. 7 These results suggest that some of the actions of 8-OH-DPAT previously ascribed to agonism at 5-hydroxytryptamine (5-HT) receptors may actually result from blockade of the actions of endogenously released noradrenaline acting on alpha 2-adrenoceptors.