Using a differential screening strategy, clone 133 was identified as an immediate early gene induced by interleukin-1 (IL-1) in human endothelial cells (HEC). The sequence of the cDNA revealed identity with a recently identified member of the inhibitors of nuclear factor kB family (IkB). IkB/clone 133 is expressed at low levels in unstimulated endothelial cells and is rapidly induced by the inflammatory cytokines IL-1 and tumor necrosis factorα(TNFα*), but not interleukin-6. Inducibility by IL-1 is abolished by the IL-1 receptor antagonist. Cycloheximide superinduces IkB/clone 133 expression in HEC. IL-1 and TNFαhave little or no effect on IkB/clone 133 expression in a fibrosarcoma cell line responsive to these polypeptide mediators. These results show for the first time cytokine-inducible lineage-specific expression of a member of the IkB family.