We have investigated the effect of 4 ganglionic cholinergic antagonists (hexamethonium, mecamylamine, pentolinium, trimetaphan) on rat alpha 3 beta 2 and alpha 3 beta 4 neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes. Current responses were elicited by fast application of acetylcholine on voltage-clamped oocytes (holding potentialVh = -80mV). Concentration-inhibition curves were used to get estimates of IC50, the antagonist concentration yielding 50% reduction of the peak current. The KB's of the antagonists were calculated using estimates of the apparent KD of acetylcholine. The order of affinity of the antagonists was similar for both receptor subtypes: mecamylamine approximately pentolinium > hexamethonium > trimetaphan. However, alpha 3 beta 4 neuronal nAChRs were 9 to 22 times more sensitive to each of the 4 antagonists than alpha 3 beta 2 receptors. These results further underline the importance of the beta-subunit as co-determinant of the functional properties of neuronal nAChRs.