In the context of studies of the ortho effect, two series of 2-monosubstituted (H, CH3, CF3, OH, CH3O, F, Cl, NH2, CN, NO2) and 2,6-disubstituted anilines (containing all combinations of CH3, CH3O, Cl, and NO2 substituents) were chosen for this work. Commercially unavailable derivatives were synthesized, and dissociation constants in water were determined for those substances for which the proper measurements had not yet been carried out. A critical compilation of pK(a) literature data has been summarized and compared with the authors' own data. The analysis and interpretation of the ortho substitution effect and its manifestation in the dissociation constants of the studied anilines (as log K,,) was based on two different approaches-correlation analysis (similarity principle) and quantum-chemistry calculations. The classical correlation equation with substituent constants sigma(1) and sigmaR was extended by the parameter v describing the steric effects, but the correlation was not close enough (s = 0.514, R = 0.986). The AISE theory (alternative interpretation of substituent effects), extended by parameter v for the steric effects description, significantly improved the correlation (s = 0.139, R = 0.9991). The B3LYP/6-311G(d,p) method was used for the calculation of physical-chemical properties of protonated and nonprotonated forms of aniline derivatives. Quantum chemically calculated properties were correlated with experimental data. The data mining regression method showed that the statistically most suitable interpreting variables are the Gibbs energy of the dissociation equilibrium (DeltaG(eq)) and the sum of the natural charges of the nonprotonated amino group hydrogen atoms (Q(n)(SigmaH)) and the dipole moment of the aniline protonated form (mu(+)). This correlation is closer (s = 0.316, R = 0.995) than that based on the similarity principle. The correlation with quantum-chemical characteristics indicates a close interrelation of the dissociation constant with the energy of the equilibrium participants and the delocalization energy of the nonprotonated form of aniline. The meaning of the SigmaH quantity in the correlation relation is related to the presence of a nitro substituent (intramolecular hydrogen bond with the reaction center). The dipole moment of the aniline protonated form mu(+) is in relation with nonspecific solvation in an aqueous medium.