The interactions between dipalmitoylphosphatidylcholine (DPPC) and the tranquilizer, chlorpromazine hydrochloride (CPZ), were studied using isothermal titration calorimetry. Results showed that the heats of interaction were different for the interactions between CPZ and DPPC small vesicles, large unilamellar vesicles, and multilayers, especially at high X, CPZ to DPPC mole ratios. In our experiments, an extruder was used to produce large, uniform unilamellar vesicles. The heats of interaction were also found to be temperature dependent. At 310 ?K, the heats were observed in the range of -2070 ?J to 10,400 ?J. This process was exothermic at X = 0.025 - 0.066, but became endothermic at X = 0.066 - 2.6. At 303 ?K, smaller endothermic heats less than 2000 ?J were observed at X = 0.025 - 2.6. Isothermal titration calorimetry provided a direct and sensitive method to study intermolecular interactions.