The lipophilicity of angiotensin converting enzyme inhibitors (ACE-I) available in France has been compared using two complementary methods. Studies have been performed both on active ACE-I and prodrugs. The first study used reverse phase high performance liquid chromatography (HPLC) in order to measure the n-octanol water partition coefficients. They were measured at 3 pH values (2.5, 4.7 and 7.4). The second study was performed on the basis of computer drawn chemical formula. The lipophilic area to hydrophilic area ratio was calculated from the three dimensional structure of each ACE-I. A calculated n-octanol water partition coefficient was then determined. Whatever the method, a broad range of values was seen. The HPLC n-octanol water partition coefficient ranged from -1.86 (captopril) to 1.02 (trandolaprilate). The lipophilic to hydrophilic ratio ranged from 1.33 (captopril) to 2.74 (trandolaprilate) and the computer determined n-octanol water partition coefficient ranged from -0.36 (perindoprilate) to 0.69 (quinaprilate). A strong correlation (r = 0.97 p = 0.0001) was found between the lipophilic/hydrophilic area ratio and the HPLC partition coefficient. The classification of the ACE-I was very close whatever the mode of determination. The less lipophilic ACE-I are lisinopril and captopril and the most lipophilic are quinalapril and trandolapril. Clinical consequences of such differences remain unknown.