A series of 2-(3- and 4-substituted phenyl)-3-[3-(N, N-dimethyl-amino)propyl]-1,3-thiazolidin-4-ones acting as H1-antihistaminics was investigated with a combined Hansch-CoMFA approach. The substituents at the 3- and 4-positions of the phenyl ring have been described through steric, electronic and hydrophobic parameters and correlated with pA2 values. The obtained quantitative models suggest that affinity to the receptor is promoted by hydrophobic and small 4-substituents and by 3- and 4-substituents generating a positive electrostatic potential towards a complementary receptor region.