Serum contains a soluble growth hormone-binding protein which is produced in some species by proteolytic cleavage of the extracellular domain of the growth hormone receptor. The hypothesis that a growth hormone-binding protein messenger RNA is produced in other species by alternative splicing of nascent growth hormone receptor transcripts was confirmed by analysis of the mouse growth hormone receptor gene. An exon that encodes the hydrophilic tail of the binding protein is located between an exon encoding the final portion of the hormone binding domain and an exon encoding the hydrophobic transmembrane domain of the receptor.