With the versatility of the molecular mechanism of amphiphilic drugs there is the possibility that ibuprofen could interact with eukaryotic model membrane lipids. Using the Langmuir technique, we first determined the pressure/molecular area isotherms of glycerophospholipids monolayers at 37 degrees C, and, second, using differential scanning calorimetry (DSC), phase transition parameters in liposomes of the same lipids. Ibuprofen interacted in a concentration-independent manner with monolayers of saturated phosphatidylcholines (PC, i.e. markers of the outer membrane leaflet of eukaryotic cells). Ibuprofen was found to interact with liposomes of saturated and unsaturated phosphatidylcholines and -serines (PS, i.e. markers of the inner membrane leaflet of eukaryotic cells), and saturated ethanolamines (PE, i.e. markers of the inner membrane leaflet of eukaryotic cells). A lowering of the lipid melting temperature (Tm) and a change of enthalpy (deltaH) of the gel to liquid-crystalline phase transitions of liposomes were detected.