A short and efficient synthesis of both enantiomers of 2,8-dimethyl-1-oxa-8-azaspiro[4.5]decan-3-one is described. The biological activity of the racemate resides predominantly in the S-enantiomer. While the S-isomer is a full M2-agonist, the R-isomer is devoid of M2 efficacy. Interest in cholinomimetics for the treatment of cognition dysfunction associated with Alzheimer's disease (AD) has been rekindled by the recent clinical use of tacrine, an acetylcholinesterase inhibitor, and advances of muscarinic agonists xanomeline 2a and WAL 20142b in clinical trials. We previously reported 3 that 1-oxa-8-azaspiro[4.5]decan-3-one (1, 4), a racemate, was a functionally non-selective but highly efficacious muscarinic partial agonist. In light of the well-known fact that enantiomers can exhibit quite different pharmacological profiles and pharmacokinetics from their corresponding racemate (5,6), the possibility exists that individual enantiomers of 1 might demonstrate unique selectivity with respect to various known muscarinic receptor subtypes. Potential differences for affinity or efficacy of the optical isomers of 1 for M1, M2, and M3 receptors would provide useful information about the unique difference in agonist interactions at these receptor subtypes during the formation of the ligand-receptor complex (binding) and receptor activation (efficacy). In this communication the synthesis and biological activity of the enantiomers of 1 will be described.