The present state of knowledge about growth hormone binding proteins (GHBP) is reviewed, with particular emphasis on the high affinity GHBP, which represents the circulating ectodomain of the growth hormone receptor (GHR). GHBP is conserved through vertebrate evolution, is produced in many tissues (especially liver) by either alternative GHR mRNA splicing (rodents) or by proteolytic cleavage from the GHR (humans, rabbits and several other species). The metailoprotease TACE (tumor necrosis factor-alpha converting enzyme) is the likely enzyme responsible for cleavage, but the structural requirements for TACE recognition or catalysis, and hence the precise cleavage point in the GHR, are unknown. GHBP is widely distributed in biological fluids, with marked concentration differences amongst them. GHBP binds about half of the circulating GH under basal conditions but is easily saturated at high GH levels; it subserves complex functions, including a circulating buffer/reservoir function for GH, prolongation of plasma GH half-life, competition with GHRs for GH, and probably unproductive heterodimer formation with the GHR. The net effect of these partly enhancing and partly inhibitory functions on GH action in vivo is complex and difficult to ascertain. Serum