THE human pituitary hormones, growth hormone (hGH) and prolactin (hPRL), regulate a large variety of physiological processes, among which are growth and differentiation of muscle, bone and cartilage cells, and lactation(1). These activities are initiated by hormone-receptor binding. The hGH and hPRL receptors (hGH(R) and hPRL(R), respectively) are single-pass transmembrane receptors from class 1 of the haematopoietic receptor superfamily(2,3). This classification is based on sequence similarity in their extracellular domains, notably a highly conserved pentapeptide, the so-called ’WSXWS box’, the function of which is controversial. All ligands in class 1 activate their respective receptors by clustering mechanisms(4). In the case of hGH, activation involves receptor homodimerization in a sequential process : the active ternary complex containing one ligand and two receptor molecules is formed by association of a receptor molecule to an intermediate 1:1 complex(5-8). hPRL does not bind to the hGH receptor, but hGH binds to both the hGH(R) and hPRL(R), and mutagenesis studies have shown that the receptor-binding sites on hGH overlap(9). We present here the crystal structure of the 1:1 complex of hGH bound to the extracellular domain of the hPRL(R). Comparisons with the hGH-hGH(R) complex(10) reveal how hGH can bind to the two distinctly different receptor binding surfaces.