A series of four racemic ring-substituted trans-2-(indol-3-yl)cyclopropylamine derivatives was synthesized and tested for affinity at the 5-HT1A receptor, by competition with [3H]-8-OH-DPAT in rat hippocampal homogenates, and for affinity at the agonist-labeled cloned human 5-HT2A, 5-HT2B, and 5-HT2C receptor subtypes. None of the compounds had high affinity for the 5-HT1A receptor, with the 5-methoxy substitution being most potent (40 nM). At the 5-HT2A and 5-HT2B receptor isoforms, most of the compounds lacked high affinity. At the 5-HT2C receptor, however, affinities were considerably higher. The 5-fluoro-substituted compound was most potent, with a Ki at the 5-HT2C receptor of 1.9 nM. In addition, the 1R,2S-(-) and 1S,2R-(+) enantiomers of the unsubstituted compound were also evaluated at the 5-HT2 isoforms. While the 1R,2S enantiomer had higher affinity at the 5-HT2A and 5-HT2B sites, the 1S,2R isomer had highest affinity at the 5-HT2C receptor. This reversal of stereoselectivity may offer leads to the development of a selective 5-HT2C receptor agonist. The cyclopropylamine moiety therefore appears to be a good strategy for rigidification of the ethylamine side chain only for tryptamines that bind to the 5-HT2C receptor isoform.