Differential scanning calorimetry, infrared spectroscopy, solid-state C-13 and H-2 NMR spectroscopy, and X-ray diffraction were used to characterize hydrated mixtures of palmitic acid (PA) and cholesterol (chol), at low (5.4) and high (8.5-9.0) pH. The pH affects the ionization state of the fatty acid, and it was found to modulate its interaction with cholesterol, and the architecture of the resulting complexes. At low pH, this system undergoes a transition from a phase-separated crystalline state to a lamellar liquid-ordered lo) phase, in agreement with previous results (Langmuir 2001, 17,5587-5594). The apparent pK(a) of PA in these conditions is found to be about 8.2. At high pH, when the fatty acid is deprotonated and consequently negatively charged, both components participate in the formation of an lo lamellar structure that was found to be stable over a large temperatre range (20-70degreesC). For 50/50 PA/chol mixtures, only this phase, Angstrom with a d spacing of approximately 49 Angstrom is detected. These fluid bilayers can be characterized as having solubilized cholesterol and highly ordered PA hydrocarbon chains. It is thus proposed that the electrostatic repulsion between carboxylate headgroups allows cholesterol molecules to integrate into the palmitate matrix. The sterol promotes the bilayer formation and leads to an ordering of the PA acyl chain, a wellknown effect of cholesterol with phospholipids. Therefore, the PA/chol system allows for the production of very simple lo lamellar structures that are pH-sensitive.