The effects of the antipsychotic drug, chlorpromazine hydrochloride (CPZ), on the phase behavior of hydrated dipalmitoylphosphatidylcholine (DPPC) have been investigated by fluorescence spectroscopy and differential scanning calorimetry. Incorporation of the amphiphilic drug into the bilayer began to dramatically affect its fluidity as low as 2 mol% CPZ. With increasing CPZ concentration, the pre- and main transition temperatures of DPPC decreased. These thermal shifts demonstrated that interactions of the tricyclic phenothiazine ring on CPZ with the lipid head groups disordered the acyl chains of DPPC such that it favors the liquid crystalline phase over the gel phase. Fluorescence anisotropy results confirmed that the acyl chain regions near the phenothiazine ring become more fluid with higher amounts of CPZ. The sub- and pretransition peaks disappeared in the presence of 5 mol% CPZ, indicating a direct transition from planar gel to the liquid crystalline phase upon destabilization of the subgel and rippled gel phases. Near 30 mol% CPZ, the appearance of a broad peak centered at 33?C suggests the induction of the interdigitated phase. Ultimately, the emission spectra of CPZ depend on the hydration of DPPC, the amount of CPZ present, and partitioning of the drug into the bilayer.