We have cloned a group of cDNAs representing mRNAs that are rapidly induced following adherence of human monocytes. One of the induced transcripts (MAD-3) encodes a protein of 317 amino acids with one domain containing five tandem repeats of the cdclO/ankyrin motif, which is 60% similar (46% identical) to the ankyrin repeat region of the precursor of NF-KS/KBFl~ 50. The C-terminus has a putative protein kinase C phosphorylation site. In vitro translated MAD-3 protein was found to specifically inhibit the DNA-binding activity of the p5O/p65 NF-KB complex but not that of the p5O/p50 KBFl factor or of other DNA-binding proteins. The MAD-3 cDNA encodes an IKE-like protein that is likely to be involved in regulation of transcriptional responses to NF-KS, including adhesion-dependent pathways of monocyte activation.