THE NF-κB subunits pSO 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 domain^1–13. Nuclear transfer of each of these factors is controlled by cytoplasmic inhibitors, and regulated by specific stimuli. The inhibitors 1κB-α and -β and pp40 recognize either p65 or the c-rel protein^14–16. 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 IκB-like molecule for native NF-κB but is specific for the p50 subunit. The ankyrin repeat domain of the bcl-3 product is shown to mediate complex formation with NF-κB dimers by contacting the conserved dimerization domain of NF-κB.