Apelin-17 is an endogenous ligand of the human orphan G protein-coupled receptor APJ, reported to act as a coreceptor of CD4 for human and simian immunodeficiency viruses. Apelin-17 and apelin-13 represent the predominant molecular forms of apelin present in the whole brain, hypothalamus, and plasma. Like apelin-13, apelin-17 exhibited a high activity on extracellular acidification rate and strongly inhibited forskolin-stimulated cAMP production in CHO cells expressing the human or the rat apelin receptor. The peptide might play a crucial role in the maintenance of body fluid homeostasis by counteracting AVP (arginine vasopressin) actions through inhibition of AVP neuron activity and AVP release.