CD200 is a type I membrane glycoprotein which is expressed on a number of cell types uniquely relevant to the inflammatory and immune cascade; included in those are dendritic cells, endothelial cells and activated T cells. Previous studies have shown that CD200 plays an important role in prevention of graft rejection, autoimmune diseases and spontaneous abortion. The molecular mechanism(s) controlling expression of CD200 are yet to be defined. We report below the cloning and characterization of the 5'-flanking region of the human CD200 gene, including an exon1/intron1 boundary region and various transcriptional initiation sites. Serial deletion analysis revealed a 169 bp region responsible for constitutive expression of CD200. Positive regulatory domains (PRDs) were identified in the core promoter using linker-scanning mutagenesis. EMSA documented clear evidence for C/EBPbeta as being important in transcriptional regulation of CD200.