1-(2,5-Dimethoxy-4-bromophenyl)-2-aminopropane (DOB; 1a) is a purported serotonin (5-HT) agonist that binds selectively to central 5-HT2 binding sites. Systematic removal of any or all of the aromatic substituents had relatively little effect on 5-HT1 binding but reduced 5-HT2 binding by approximately 2 or more orders of magnitude. Demethylation of the 2-methoxy group of 1a, or introduction of an N-n-propyl group, doubled 5-HT1-site affinity but decreased 5-HT2-site affinity by 3- and 30-fold, respectively. In tests of stimulus generalization, using rats trained to discriminate DOM from saline, the 2-demethyl and N-propyl derivatives were found to produce stimulus effects similar to those of DOB. In addition, the S-(+) isomer of the iodo analogue of 1a was found to possess one-third the affinity of its R-(-) enantiomer at 5-HT2 sites and also resulted in DOM-stimulus generalization. Of the DOB analogues examined, DOB (1a) possesses optimal selectivity for 5-HT2 binding.