A new method to quantify the substituent effect, called "3D correlation anal." (3D-CAN), is presented. This approach employs an at. level of consideration of substituent effects and is developed on the basis of empirical inductive and steric constants However, unlike traditional correlation anal., 3D-CAN takes into account the three-dimensional structure of substituents. Extensive datasets of exptl. dissociation constants for a broad range of carboxylic acids and protonated amines (including a number of polypeptides) have been accurately reproduced in the framework of the developed novel technique. New formulas allowing calculation of pKa values for 826 carboxylic acids and 802 protonated amines have been established, and the possibility of interpretation of the phys. nature of the substituent effects within the framework of 3D-CAN is presented in the present paper. This validates the methodol. as a powerful technique broadly applicable to general reaction phenomena.