Prostaglandin E₂is 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. EP₁expression predominates in the collecting duct where it inhibits Na⁺absorption, contributing to natriuresis. The EP₂receptor regulates vascular reactivity, and EP₂receptor-knockout mice have salt-sensitive hypertension. The EP₃receptor 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. EP₄mRNA is expressed in the glomerulus and collecting duct and may regulate glomerular tone and renal renin release. The capacity of PGE₂to bidirectionally modulate vascular tone and epithelial transport via constrictor EP₁and EP₃receptors vs. dilator EP₂and EP₄receptors allows PGE₂to serve as a buffer, preventing excessive responses to physiological perturbations.