CD99 and CD99 like 2 protein (CD99L2) are membrane glycoprotein leukocyte antigens that do not belong to any known protein family. They are expressed at the endothelial cell junction and are known to participate in the diapedesis process. Using mouse CD99 and CD99L2 gene, we show that CD99 interact with CD99L2. To examine molecular interaction between mouse CD99 and mouse CD99L2 and to localize the site of the interaction, we used a bimolecular fluorescence complementation (BiFC) assay via flow cytometry and confocal analysis. The interaction between mouse CD99 and mouse CD99L2 was verified by isothermal tiltration calorimetry (ITC) and coimmunoprecipitation. The interaction between CD99 and CD99L2 proteins is mediated by cytoplasmic domain of CD99. Their interaction enhanced the localization of each protein to the cell surface membrane and also increased cell-cell interaction via homophilic way. The results from this study suggest that the interaction of CD99 and CD99L2 may control the location and functions of CD99 and CD99L2 as cell adhesion molecules. *This study is supported by a fund from national research foundation (2007-2003619), republic of Korea.