Arginine vasopressin (AVP)-stimulated cAMP generation is decreased in the immature collecting duct (CD). This is the result of prostaglandin antagonism, most likely via the inhibitory guanine nucleotide-binding protein (G(i)). The EP(3)-subtype prostaglandin E(2) (PGE(2)) receptor, which is coupled to G(i), could mediate this effect. We studied the developmental expression of EP(3) receptor in the rabbit kidney. Higher levels of EP(3) mRNA were observed in the immature kidney using three different assays: I) reverse transcription-polymerase chain reaction (RT-PCR) with internal standard, 2) competitive PCR, and 3) ribonuclease protection assay. The highest levels were observed at 2 wk of age. RT-PCB from isolated nephron segments detected EP(3) mRNA in the medullary thick ascending limb, cortical CD (CCD), and inner medullary CD (IMCD)) of adult and immature kidneys. We conclude that I) renal expression of EP(3) mRNA is increased in immature kidneys and 2) EP(3) mRNA is localized in the distal nephron. This suggests that EP(3) receptor may play a role in the regulation of distal tubular transport during development.