Like other phenylisopropylamine derivatives, 4-methylaminorex is a central stimulant. The cis isomer of 4-methylaminorex ("U4Euh"; "ICE") has appeared on the clandestine market as a novel designer drug and was recently classified as a Schedule I substance. In the present investigation, the stimulus properties of racemic cis, racemic trans, and all four individual optical isomers of 4-methylaminorex were examined in rats trained to discriminate 1 mg/kg of S(+)amphetamine sulfate from saline. The S(+)amphetamine stimulus generalized to all of the agents investigated and the relative potencies of the optical isomers (followed by ED50 values) were as follows: trans(4S,5S) (0.25 mg/kg) greater than cis(4S,5R) (1.2 mg/kg) = cis(4R,5S) (1.5 mg/kg) greater than trans(4R,5R). The trans(4R,5R) isomer did not completely substitute for S(+)amphetamine unless a longer (i.e., 60-min) presession injection interval was used, suggesting that it has a longer duration of onset than the other isomers of 4-methylaminorex. The results, which are consistent with established structure-activity relationships, suggest that the trans(4S,5S) isomer (which has not been scheduled) is similar in potency to (+)amphetamine (ED50 = 0.4 mg/kg) and is more potent than either of the cis isomers.