The quantitative structure-activity relationship (QSAR) of 2-alkyl-4-(biphenylylmethoxy) pyridine derivatives was studied.Three different alignment methods were used to get the models of the comparative molecular field analysis (CoMFA),the comparative molecular similarity indices analysis (CoMSIA),and the hologram quantitative structure-activity relationship (HQSAR).The statistical results from the established models show believable predictiviry based on the cross-validated value (q2＞0.5) and the non-validated value (r2＞0.9).The analysis on contour maps of CoMFA and CoMSIA models suggests that hydrophobic and hydrogen-bond acceptor fields are important factors that affect the AT1 antagonistic activity of 2-alkyl-4-(biphenylylmethoxy) pyridine derivatives besides the steric and electrostatic fields,The structural modification information from different atom contributions in the HQSAR model is in agreement with that in the 3D-QSAR models.