Two overlapping cDNA clones encoding the sheep growth hormone (GH) receptor were isolated from a sheep liver cDNA library. The translated amino acid sequence predicts a polypeptide precursor of 634 amino acids with a calculated molecular weight of 70,799. The mature GH receptor comprises an extracellular domain of 242 amino acids, a hydrophobic transmembrane region of 24 amino acids, and a cytoplasmic domain of 350 amino acids. The nucleotide and translated amino acid sequences display extensive similarity with sequences established for GH receptors from a number of other mammalian species. A prominent transcript of 4.5 kb and a minor transcript of 1.9 kb are detected following Northern blot hybridization of poly(A)+ RNA isolated from sheep liver. The onset of GH receptor mRNA expression in the liver is developmentally regulated: GH receptor transcripts are first detected by Northern blot hybridization in liver taken from a term (145 days of gestation) fetus and reach maximum levels within one week following birth. Ribonuclease protection assays reveal heterogeneity within the 5' untranslated region of GH receptor mRNA transcripts detected in liver and a number of other tissues. At least one transcript appears to be expressed in a liver-specific fashion, supporting a role for alternative RNA splicing in the tissue-specific regulation of sheep GH receptor expression.