Prostaglandin E₂ is a major renal cyclooxygenase metabolite of arachidonate and interacts with four G protein-coupled E-prostanoid receptors designated EP₁, EP₂, EP₃, and EP₄. Through these receptors, PGE₂modulates renal hemodynamics and salt and water excretion. The intrarenal distribution and function of EP receptors have been partially characterized, and each receptor has a distinct role. EP₁ expression predominates in the collecting duct where it inhibits Na⁺ absorption, contributing to natriuresis. The EP₂ receptor regulates vascular reactivity, and EP₂ receptor-knockout mice have salt-sensitive hypertension. The EP₃ receptor is also expressed in vessels as well as in the thick ascending limb and collecting duct, where it antagonizes vasopressin-stimulated salt and water transport. EP₄ mRNA is expressed in the glomerulus and collecting duct and may regulate glomerular tone and renal renin release. The capacity of PGE₂ to bidirectionally modulate vascular tone and epithelial transport via constrictor EP₁ and EP₃ receptors vs. dilator EP₂ and EP₄ receptors allows PGE₂ to serve as a buffer, preventing excessive responses to physiological perturbations.