We have studied the effect of mono- and di-valent cations on the structure of the phosphatidylinositol 4,5-diphosphate (PIP2)–biological buffer system at pH 7.2. We found that the PIP2 aggregates from prolate ellipsoidal micelles at pH 7.2 and that the addition of a small amount of Ca2+ ions even below 5 mmol dm–3([Ca2+] : [PIP2]= 5/7) induces a drastic structural phase transition from prolate micelles to disordered lamellae. Mg2+ ions induced a similar phase transition around 10 mmol dm–3, which, however, occurred less sensitively. In contrast to the case of divalent cations, the presence of Na+ ions did not affect the PIP2 micellar structures up to 0.1 mol dm–3([Na+] : [PIP2]= 100/7), indicating that the above structural change of the PIP2 aggregates is not attributable to the elevation of the electrostatic shielding effect between the polar heads. Modelling analysis suggests that the observed phase transition results from an increase of the critical packing parameter of the PIP2 molecule accompanying the dehydration of the PIP2 polar-head region.