Interactions between the polysaccharide chitosan and negatively charged phospholipid liposomes were studied as a function of compositional and environmental conditions. Using isothermal titration calorimetry, different levels of deprotonation of chitosan in acidic solutions were attained with titration of the fully protonated polymer at pH 4.48 into solutions with increasing pH. The process was found to be highly endothermic. We then examined the interaction of the polymer with vesicles in solutions of different pH. Even when partially deprotonated, the chitosan chains retain their affinity to the negatively charged liposomes. However, the stronger adsorption results in lower organization of the chains over the membrane.