The interactions of n-butanol with dipalmitoylphosphatidylcholine (DPPC) were studied using titration calorimetry and differential scanning calorimetry (DSC). DSC results indicated that n-butanol induces the interdigitated phase in DPPC above 10 mg/mL butanol. A new application of titration calorimetry for measuring partition coefficients of nonsaturating solutes into lipids was developed. The partition coefficients and the heat of binding of n-butanol into DPPC were measured for the L(beta)', P(beta)', L(alpha), and L(beta)I phases of DPPC. The partition coefficients were temperature dependent and ranged from 70 to 110 for the L(beta)I phase, from 170 to 183 for the L(alpha) phase, and similar to that for the L(beta)I phase in the P(beta)' phase. The binding to the L(beta)' phase could not be detected, giving an upper limit for this partition coefficient of 23. The enthalpies for binding to the L(beta)I and L(alpha) phases were 1.0 and 1.5 kcal/mol, respectively. The van't Hoff enthalpy was in good agreement with the calorimetric enthalpy for the partitioning into the L(alpha) phase; however, it was greater than the calorimetric enthalpy for the L(beta)I phase, suggesting that the interaction of n-butanol with this phase is cooperative in some way.