Three-dimensional quantitative structure-activity relationships (3D QSAR) are widely used for the prediction of in vitro or in vivo interactions between chemical compounds and their biological targets (transporters, receptors, ion channels, enzymes). Comparative receptor surface analysis (CoRSA) is a new 3D QSAR algorithm that can be applied to study ligand-receptor interactions whenever the structure of the biological target is not known. The steric and electrostatic features of the most active compounds from a QSAR set are used by CoRSA to generate a virtual receptor model, represented as points on a surface complementary to the van der Waals surface of the aligned compounds. The CoRSA structural descriptors, represented by the total interaction energies between each surface point of the virtual receptor and all atoms in a molecule, are used in a partial least squares data analysis to generate a structure-activity model. In this paper the calcium channel antagonist activity of 35 dihydropyridine derivatives is modeled with CoRSA, giving a 3D QSAR with r2 = 0.928 for calibration and r2cv = 0.921 for the leave-one-out cross-validation.