Receptors for growth hormone (GH) and prolactin (PRL) belong to the GH/PRL/cytokine receptor family, characterized by a unique transmembrane domain and absence of intrinsic tyrosine kinase. The GH receptor (GHR) is a protein of 620 amino acids; the extracellular domain of 246 amino acids is made of two subdomains, one being the domain of interaction with the ligand, the second one being the region of association with another receptor resulting in a homodimer. In addition to the membrane-bound receptor, a soluble form, called the GH-binding protein (GHBP), has been identified in the serum and corresponds to the extracellular domain of the full-length receptor. Two mechanisms of generation for the GHBP exist. In rodents, a 1.2-kb mRNA encodes the GHBP and its hydrophilic C-terminal sequence. In man and many species, no specific mRNA for the GHBP is detected: only one form of mRNA of 4.5 kb encoding the membrane GHR is found by Northern blot analysis. GHBP probably results from proteolytic cleavage of the membrane receptor. Plasma GHBP has a high binding affinity for the hormone comparable to that of the liver GHR. Half-life is longer for GH bound to the binding protein than for free GH. GH-GHBP complex represents a hormone reservoir. Other functions for GHBP remain to be clarified. Plasma levels of GHBP probably reflect the concentration of liver GHRs. Levels of liver GHR and plasma GHBP have been shown to change in parallel. GHBP measurements help in understanding situations of GH resistance. Many factors play a role in the regulation of the plasma GHBP which has been shown to change with age and nutritional status. GH, insulin and sex steroids also influence plasma GHBP levels. No PRL-binding protein has been detected in serum. In rabbit milk a soluble PRL receptor has been identified. The mechanism of its generation and its exact function has to be clarified.