The X box is an essential transcriptional regulatory region for both constitutive and inducible expression of HLA-class II genes, and, while highly conserved among class II genes, both locus- and allele-specific polymorphisms exist. Using gel regardation analysis, we have analyzed the binding of B cell nuclear proteins to the X box regions of the DQB1 *0302, *0301, and DRA genes and have identified two distinct X box binding complexes which differ for the diabetes-associated DQB 1*0302 allele.