Increase of lipophilicity of cationic doxorubicin (DOX) by its association with a fatty acid ion is of interest for pharmaceutical formulations and could have an impact on the drug delivery into cancer cells. On the basis of spectroscopic analysis of intrinsic DOX fluorescence, this study provides an experimental evidence of DOX-oleate interactions as function of ion/drug molar ratio (R) and pH. An electrostatic attraction to oleates is dominant for the cationic form of DOX (pH 6.5) and a hydrophobic interaction is characteristic of the molecular form of DOX (pH 8.6). A high content of sodium oleate vesicles ([oleate]>/=0.2 mM, R>/=20) limits the electrostatic and hydrophobic interactions at pH 6.5 while favoring the hydrophobic interactions at pH 8.6. The influence of these interactions on the lipophilicity of the cationic form of DOX is analyzed by measuring the apparent partition coefficient (aqueous buffer pH 6.5/methylene chloride). The results show a lipophilicity gain for the cationic form of DOX in presence of 10 : 1 ion/drug molar ratio, while no lipophilicity increase is observed at 50 : 1 molar ratio.