The present study was conducted to determine if the tetracyclic antidepressant mianserin could be established as a discriminative stimulus in rats. One group of rats was trained to discriminate mianserin (4.0 mg/kg, IP) from saline in a two-lever drug discrimination procedure, and a second group of rats was trained to discriminate the muscarinic cholinergic antagonist scopolamine (0.25 mg/kg, IP) from saline. Generalization testing with the training drugs yielded an ED50 of 0.502 mg/kg for the mianserin-trained rats and an ED50 of 0.048 mg/kg for the scopolamine-trained rats. Asymmetrical cross-generalization between mianserin and scopolamine was observed, because scopolamine produced mianserin-appropriate responding, but mianserin did not produce scopolamine-appropriate responding. This study is the first demonstration that rats can be trained to discriminate mianserin from saline and that antagonism of muscarinic cholinergic receptors is sufficient to produce mianserin-appropriate responding.