Rats were trained in a two-lever operant procedure to discriminate either 1.0 mg/kg (+)amphetamine or 1.5 mg/kg DOM from saline. Rats trained to discriminate DOM from saline showed generalization with the DOM training condition when tested with mescaline or 2,5-dimethoxy-4-ethylamphetamine (DOET), but not when tested with (+)amphetamine or methylphenidate. Both isomers of DOM generalized with racemic training compound, the (-)isomer being more potent. The DOM stimulus was completely blocked by the serotonin (5-HT) antagonists cinanserin and methysergide, but not by the peripheral 5-HT antagonist xylamidine nor the dopamine antagonist haloperidol. Rats trained to discriminate (+)amphetamine from saline generalized with the amphetamine training condition when tested with methylphenidate but not when tested with mescaline, DOET, racemic DOM, or either isomer of DOM. The amphetamine stimulus was blocked by pretreatment with haloperidol but not by cinanserin, methysergide, or xylamidine. The results show that, despite their structural similarity, amphetamine and DOM induce pharmacologically distinct stimuli.