The optical rotation of natural amino acids becomes more positive when the medium is changed from approximately neutral to strongly acidic (Clough–Lutz–Jirgensons (CLJ) effect). In this work, it is shown by time–dependent density functional computations that the effect can be generalized to other α–substituted chiral carboxylic acids. The physical origin of the generalized CLJ effect is similar to that in amino acids, linking the absolute configuration directly to the sign of CLJ. For conformationally flexible molecules with small magnitudes of the optical rotation, the presence of a CLJ effect might aid the assignment of absolute configurations based on comparing experimental data with computed chiroptical responses. Chirality, 2010. © 2010 Wiley‐Liss, Inc.