Transforming growth factor-α (TGF-α) is a 50-amino acid polypeptide synthesized as part of a larger precursor of 159 amino acids. Its expression has been reported in normal and neoplastic kidney. In this report, we characterized a renal TGF-α-immunoreactive protein, which we named TGF-α-related protein (TGF-α-RP). It was found to be present in the final part of the collecting tubules of the normal rat kidney. Western blotting analysis of kidney samples revealed a protein of 38 kD and pI = 5.5. In nonreducing conditions immunoreaction for this protein decreased and a TGF-α-immunoreactive protein of 150 kD was observed. The expression of TGF-α-RP seems to be highly conserved in the kidney of mammals and chickens. Therefore, TGF-α-RP may have an important role in the normal development and function of the kidney.