This study focuses on mixtures of phosphatidylethanolamines with the monofluorinated phospholipid 1-palmitoyl-2-[16-fluoropalmitoyl]sn-glycero-3-phosphocholine (F-DPPC). Specifically, the influence of 1,2-didodecanoyl-sn-glycero-3-phosphoethanolamine (DLPE) on the phase behavior of F-DPPC was examined. In aqueous solution, F-DPPC interdigitates without the use of an inducing agent. In contrast, because of the ethanolamine head group, the interdigitated phase in phosphatidylethanolamines is highly unfavorable. Differential scanning calorimetry (DSC) was used to analyze the thermotropic phase behavior and miscibility of these lipids. In addition, fluorescence spectroscopy using the probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to detect interdigitation. Spectrophotometry experiments were also used to analyze the phase behavior of this lipid system. Both DSC and spectophotometry results demonstrate that F-DPPC/DLPE mixtures are highly miscible between 0 and 70% F-DPPC as indicated by a single transition peak in heating and cooling scans. However, at concentrations above 70% F-DPPC, two peaks emerge, suggesting the lipids begin to separate into two separate domains. Similarly, the main transition temperature of the mixtures increases slightly between 0 and 70% F-DPPC while a much more significant increase occurs between 70% and 100% F-DPPC. Fluorescence intensity and polarization experiments suggest that the lipid system undergoes a significant change in phase behavior at around 70% F-DPPC. As a result of its shorter chain length and ethanolamine head group, DLPE significantly disrupts the phase behavior of F-DPPC and may inhibit the interdigitated phase.