Bright is an ARID family transcription factor that increases immunoglobulin heavy chain transcription. In the mouse, Bright expression is tightly regulated and B cell-restricted and the Bright protein associates with Bruton's tyrosine kinase (Btk), the defective enzyme in X-linked immunodeficiency. Human X-linked agammaglobulinemia results from defects in Btk and leads to early blocks in B lymphocyte development. Because so little is known about human Bright, we sought to determine where human Bright is expressed in normal B cell differentiation and whether it also forms complexes with Btk. Although human and mouse Bright exhibited similar expression patterns in normal B cells, many human transformed B cell lines did not express Bright protein. However, the human protein bound prototypic Bright DNA-binding motifs and, like mouse Bright, was capable of associating with Btk. These data suggest potentially important similarities exist in Bright expression and activity in human and mouse B lymphocytes.