The neuroleptic drug spiperone (1) has proven very useful in the characterization of putative serotonin (5-hydroxytryptamine, 5-HT) receptors. Thus, 5-HT1 receptors have been divided into subtypes based on their affinities for 1: 5-HT1A sites have high affinity, while 5-HT1B sites have low affinity. However, the usefulness of 1 for the pharmacological characterization of 5-HT1A sites is limited because of its high affinity for 5-HT2 (as well as D2-dopaminergic) receptors. A close analogue of 1, (+/-)-spiroxatrine (2), has much higher affinity for 5-HT1A receptors and much lower affinity for 5-HT2 receptors. We report here the stereospecific synthesis of (R)-(+)- and (S)-(-)-spiroxatrine enantiomers and their evaluation at several 5-HT receptors and D2-dopaminergic and alpha 1-adrenergic receptors.