PAF is a powerful phospholipid-derived autacoid involved in many physio-pathological mechanisms. Many PAF antagonists have been synthesized and assayed for therapeutic purposes. In this study, molecular electrostatic potential is used to compare the electronic properties of 48 heterocyclic sp 2 nitrogen highly potent PAF antagonists, belonging to six series (nine hetrazepines, five pyrrolo[1,2-c]thiazoles, 14 carboxamides, nine dihydropyridines, nine pyridinylthiazolidines and two imidazo[4,5-c]pyridines). Their common features consist of three main electronegative zones (A, B 1 and B 2 ) describing the electronic pharmacophore of these ligands. The high affinity of these PAF antagonists seems to be related to this electronegative system A-B ( x ) , which is characterized by three distances A-B 1 (9.3 ± 1.0 ), A-B 2 (13.4 ± 0.7 ) and B 1 -B 2 (4.9 ± 0.9 ). Moreover, B 1 and B 2 may surround a common anchorage point in the binding site of the receptor.