Abstract The effects of nicotine and hexamethonium on postganglionic discharges elicited by tetanic preganglionic stimulation or muscarinic agonists were observed on the isolated hamster stellate ganglion. The amplitude and duration of the afterdischarges from tetanic preganglionic stimulation in hexamethonium (10 −3 M) were smaller than the amplitude and duration of the afterdischarges in nicotine (10 −3 M). Also, hexamethonium decreased the amplitude and duration of the afterdischarges from repetitive stimulation in the presence of nicotine. The mechanism of these effects was explored. After application of nicotine for 30 min, the discharges from McN-A-343, a muscarinic agonist, were the same as before the nicotine. Hexamethonium did not reverse the block of the single evoked potential by nicotine. The potentials during a train in the presence of hexamethonium plus atropine were the same as the potentials during a train in the presence of nicotine plus atropine. Hexamethonium did depress the McN-A-343 discharges in the presence of nicotine and also in the control solution. These results indicate that hexamethonium has a direct depressant effect on the muscarinic synaptic membrane.