Technical Abstract: Bayrepel, 2-(2-hydroxyethyl)-1-piperidine carboxylic acid-1-methylpropyl ester, and 220, 1-(cyclohex-3-ene-1-ylcarbonyl)-2-methylpiperidine have two chiral centers, and each of the four isomers has repellent activity. The degree of mosquito repellency of these stereoisomers individually and as racemic pairs has been quantified by the United States Department of Agriculture. Computational chemistry was used to identify the structural and configurational basis for repellent activity. Molecular overlay of the optimized geometries of the lowest energy conformers of the configurational isomers was investigated as a method to elucidate the role of chiral centers in 220 and Bayrepel. It was found that the presence of a chiral carbon alpha to the nitrogen with the S-configuration in the piperidine ring is essential to the three-dimensional arrangement of the atoms of the pharmacophore for effective repellent activity.