In this communication, we present the results involving the synthesis and initial pharmacology of the individual enantiomers of 5-methoxy-3-[(N-methylpyrrolidin-2-yl)methyl]indole (1), a conformationally restricted analog of serotonin. In 1, the C-N bond of the aminoethyl side chain of serotonin has been conformationally restricted into a pyrrolidine ring, and using 1 we can study the pharmacological consequences of this introduction of a stereogenic center α to the basic nitrogen in serotonin. (R)-5-methoxy-3-[(N-methylpyrrolidin-2-yl)methyl]indole (1R, CP-108,509) binds to 5-HT1A, 5-HT1C, and 5-HT2 receptors with an affinity and efficacy which is comparable to that of the natural substrate, serotonin. 1R is only slightly less potent than serotonin at 5-HT1D receptors. The S enantiomer of this compound (1S) has significantly less affinity for all 5-HT receptors (approximately 20-fold less) than either its R enantiomer or serotonin. This pair of enantiomers demonstrates the first indication of stereogenic differentiation of ligands by serotonin (5-HT1 and 5-HT2) receptors. The (R)-3-[(N-methylpyrrolidin-2-yl)methyl] group in 1R is a conformationally restricted replacement for the 3-(2-aminoethyl) group in serotonin at 5-HT1A, 5-HT1D, 5-HT1C, and 5-HT2 receptors. The novel structure of 1R provides a potentially useful pharmacological tool which can be used to study the molecular recognition phenomena of individual serotonin receptors.