AbstractThis paper reports on cDNA coding for the 80‐kDa murine IL 6 receptor (mIL 6R) that was cloned from a mouse liver cDNA library. Human hepatoma Hep3B cells transfected transiently or stably with an expression vector carrying the entire coding region for mIL6R become responsive to mouse IL 6 (mIL 6). We monitored response to the cytokine through the transcriptional activation of a co‐transfected IL 6‐inducible human C‐reactive protein (CRP) promoter; response to mIL 6 is lost upon treatment of the cells with increasing amounts of a monoclonal antibody to mIL 6R. mIL 6R mutants have been generated in the carboxy‐terminal portion of the molecule. Their functional analysis in hepatoma cells shows that the intracytoplasmic domain of the receptor is not absolutely essential to IL 6 signal transduction (i.e. CRP promoter activation), but that the last 40 amino acids contribute to maximal IL 6 response in these cells.