THE NF-kappa-B subunits p50 and p65 and the product of the rel proto-oncogene are members Of a growing class of transcription factors with a unique DNA-binding and dimerization domain1-13. Nuclear transfer of each of these factors is controlled by cytoplasmic inhibitors, and regulated by specific stimuli. The inhibitors I-kappa-B-alpha and -beta and pp40 recognize either p65 or the c-rel protein14-16. We show here that the proto-oncogene bcl-3, believed to be involved in certain human B-cell leukaemias17, encodes a protein that functions as an I-kappa-B-like molecule for native NF-kappa-B but is specific for the p50 subunit. The ankyrin repeat domain of the bcl-3 product is shown to mediate complex formation with NF-kappa-B dimers by contacting the conserved dimerization domain of NF-kappa-B.