Transcription factor NF-kappa B regulates the expression of a plethora of genes. The activity of NF-kappa B proteins is regulated by I kappa B proteins. We report that induction of I kappa B alpha, a member of the I kappa B family of proteins, is preceded by activation of NF-kappa B complex. The promoter of the I kappa B alpha gene contains a kappa B site that is directly involved in its induction by the NF-kappa B complex. Degradation of I kappa B alpha protein precedes activation of NF-kappa B DNA binding activity, whereas newly synthesized I kappa B alpha protein inhibits NF-kappa B activity. If the degradation of I kappa B alpha is prevented, the induction of DNA binding activity of NF-kappa B complex is severely curtailed. These data suggest the existence of an autoregulatory loop whereby I kappa B alpha regulates the activity of transcription factor NF-kappa B, which in turn regulates the I kappa B alpha activity.