The chromatographic properties for nine antipsychotic drugs: chlorpromazine, chlorprothixene, clozapine, quetiapine, perazine, perphenazine, prochlorperazine, promazine and trifluoperazine were studied using planar chromatography. Both C18-bonded silica gel and diol-bonded phase were used as stationary phases. Mixtures of methanol–water and tetrahydrofuran–water were investigated as mobile phases. Molecular descriptors were calculated using HyperChem, ChemAxon and ACD/labs software. The study was based on multiple linear regression and the results were presented as quantitative structure–retention relationships equations. Furthermore, both principal component and cluster analysis were performed. The classification methods showed clear differences between calculated and chromatographic established lipophilicity. Chromatographic parameters were similar to bulkiness-related, geometrical descriptors and topological indexes. On the other hand, the electronic descriptors which were strongly connected with the computational log P values had lower impact on chromatographic parameters.