Aberrant activation and expression of genes is the major cause of many human diseases. Most genes are quiescent or have minimal activity in affecting physiologic processes. However, in certain pathologic conditions, these genes are abruptly turned on by a preexisting genetic switch, causing them to overexpress. The nuclear transcription factor-kB (NF-kB) is one such important factor that controls the genetic switch for many important genes that encode cytokines, growth factors, adhesion molecules, and some acute phase proteins (1). Abnormal activation of NF-kB is associated with a number of diseases, including immune and inflammatory diseases (see Ref. 2 for review). Because of its pathophysiologic importance, the NF-kB has been identified as a key target for pharmacologic manipulations. The purpose of this study is to investigate a gene inhibition approach using synthetic peptides that inhibit signal-induced degradation of the NF-kB inhibitory subunit IkB by IkB kinases (IKK), thereby preventing NF-kB activation.