A cDNA clone derived from a human hepatocellular carcinoma has been isolated on the basis of homology to the alpha human retinoic acid receptor (RAR alpha) gene. Expression of this cDNA produces a high affinity nuclear binding protein for retinoic acid. The product of this clone when expressed in transfected cells is able to activate transcription of a reporter plasmid through specific DNA sequences in response to the addition of retinoic acid to the medium. Dose-dependent profiles upon trans-activation of the reporter indicate that apparent sensitivity to retinoic acid of this protein is approximately 10-fold higher than that of human RAR alpha and is comparable to that of the second human RAR, RAR beta. This gene has been mapped to human chromosome 12, which is distinct from those coding for either alpha or beta RAR, and thus encodes a third human RAR.