The inhibitory effect of clonidine (non-selective α 2-adrenoceptor agonist) and oxymetazoline (α 2A-adrenoceptor selective agonist) was compared on basal and stimulated gastric motor activity (gastric tone and contractions) using the balloon method in the rat. It was shown that oxymetazoline (0.2–1.7 μmol/kg, i.v.) decreased the basal motility, while clonidine (1.9–3.8 μmol/kg, i.v.) failed to affect it. When motility was stimulated centrally by insulin (5 IU/rat, i.v.), both clonidine (1.9–3.8 μmol/kg, i.v.) and oxymetazoline (0.1–3.4 μmol/kg, i.v.) inhibited the gastric motor activity. However, while the effect of clonidine was antagonized by the non-selective α 2-adrenoceptor antagonist yohimbine (5 μmol/kg, i.v.) and the α 2A-adrenoceptor selective antagonist BRL 44408 (3 μmol/kg, i.v.), the effect of oxymetazoline was only partially affected. Prazosin (α 1- and α 2B-adrenoceptor antagonist, 0.07–0.28 μmol/kg, i.v.) also failed to reverse the effect of oxymetazoline. Furthermore, when gastric motility was stimulated peripherally by activation of postsynaptic cholinergic muscarinic receptors by the combination of carbachol (0.14 μmol/kg, i.v.) and hexamethonium (37 μmol/kg, i.v.), clonidine (3.8 μmol/kg, i.v.) failed to affect the increased motor activity, however, oxymetazoline (0.8–3.4 μmol/kg, i.v.) exerted a pronounced inhibition. These results suggest that different mechanisms may be involved in the inhibitory effect of clonidine and oxymetazoline; while clonidine reduces the gastric motility by activation of presynaptic α 2-adrenoceptors, postsynaptic component in the effect of oxymetazoline has also been raised.