Inhibition of prostaglandins (PGs) synthesis induces responses on renal function that are age-dependent. Indomethacin in the adult rat potentiates the response to vasopressin whereas in the newborn rat blocks the response to dehydration. These differences suggest that the sensitivity of the renal tissue to PGs changes as the animal matures. This study was designed to analyze the characteristics of the receptors to PGE2 in the developing rat and to compare with that of the adult rat. Binding was performed in cortical and medullary slices incubated with tritiated PGE2. It was found that the renal uptake of the radioactive ligand had three components, the first is the synthesis of endogenous prostaglandins, the second is tubular secretion (only in cortex) and the third is binding to receptor sites. We found it necessary to eliminate the first two components (with indomethacin and p-amino-hippurate) to achieve an adequate measurement of the apparent affinity of the binding sites to PGE2. Under these conditions the cortex bound more PGE2 than the medulla (at all ages) and the highest affinity was observed in the neonatal cortex. Synthesis of prostaglandin E2 was higher in newborn than in adult rats. In vivo, indomethacin and acetaminophen blocked the response of the newborn rat to dehydration whereas in the weaning and adult rat the response was not changed by these inhibitors of the synthesis of prostaglandins. Our results suggest a major role of the prostaglandins in the regulation of the water balance in the neonate.