Two erbA homologs, termed ear-1 and ear-7, are present in the human genome on chromosome 17. The two genes reside in the same genetic locus with overlapping exons and are transcribed from opposite DNA strands. In addition, the ear-7 mRNA is alternatively spliced to generate two protein isoforms, namely the ear71 and ear72 proteins. Nucleotide sequence analysis predicts that the ear71 protein is a human counterpart of the chicken c-erbA protein, a molecule closely related or identical to thyroid hormone receptor. Indeed, Scatchard analysis of proteins synthesized in vitro indicated very high affinity binding of T3 to the ear71 protein but not to the ear72 protein. Interestingly, the ear-1 gene product showed low, but appreciable, binding to T3, although its authentic ligand remains to be clarified.