Addition of equimolar concentrations of chloroquine (I) [54-05-7] to dimyristoyl-, dipalmitoyl- (DPPC), or distearoylphosphatidylcholine liposomes showed an inverse linear relation between percentage reduction in transition enthalpy (ΔH) and chain length, as observed from calorimetric studies, suggesting maximum interaction of I with a membrane of greatest lipophilic character.Increasing I concentration in DPPC liposomes reduced the height of and broadened the main endothermic peak; the pretransition peak was abolished by 10-1M I.Addition of 10% stearylamine or dicetylphosphate (charged lipids) almost abolished the main endothermic peak; I (10-1M) increased ΔH but failed to restore it to the pure DPPC value; thus, I probably competes with ionic lipids for the same bilayer sites.Sonication reduced ΔH; molar I addition potentiated this.Proton NMR spectroscopy studies confirmed that I base is predominantly associated with the hydrocarbon interior of the membrane.