p27(Kip1) is one of the key regulatory proteins in cell cycle through inhibition of pRB phosphorylation by suppression of the activity of several cyclin/Cdk complexes. The expression of p27(Kip1) has been shown to be controlled by a posttranslational mechanism, although vitamin D-3 and neuronal differentiation can also induce its mRNA. Recently, the p27(Kip1) promoter was isolated and sequenced from a human leukocyte genomic library. In this report, we demonstrate that IFN alpha 2b, activates the human p27(Kip1) promoter-driven luciferase reporter gene in transient expression assays in H82 cells, This induction might involve two IRF 1-like binding sites present in the p27(Kip1) promoter. To our knowledge this is the first report on the direct activation of the human p27(Kip1) promoter by IFN alpha 2b.