The current policy of drug regulatory authorities demanding that pharmaceutical companies justify their reasons for preferring drugs containing a mixture of enantiomers over one stereoisomer increases the importance of quantitative structure-activity relations (QSARs) for chiral drugs. The QSAR proposed by Pfeiffer for chiral drug enantiomer potencies was brought into question by the existence of sets obeying an anti-Pfeiffer rule. Using computer-aided molecular design methods and treating chirality not as an existing/nonexisting property but as a continuous one improve the QSAR proposed by Pfeiffer, yielding higher correlation coefficients and an independent ordinate. Calculated shape similarities reveal the details of the Pfeiffer behavior and the source of the anti-Pfeiffer behavior. Consequently revised models for the D2 and sigma receptor are suggested.