A cDNA clone encoding a novel epidermal growth factor (EGF)-related growth regulator, epiregulin, was isolated from a cDNA library prepared from a mouse fibroblast-derived tumor cell line, NIH3T3/clone T7. The predicted amino acid sequence revealed that the purified epiregulin peptide of 46-amino acids was synthesized as an internal segment of a 162-amino acid putative transmembrane precursor. The structural organization was similar to that of TGF-alpha precursor among the members of the EGF family. Although epiregulin transcript was not detected in several adult normal tissues by Northern blot analysis, approximately 4.8-kb transcript was present in 7-day-old mouse embryo and then diminished to very low or undetectable levels. Our results suggest that epiregulin may play an important role in the regulation of epithelial cell growth during early development.