The prostaglandin system influences renal sodium and water excretion and appears to be more active in the Dahl salt-resistant (DR) than salt-sensitive (DS) rat. During an investigation of renal papillary prostaglandin E (PGE) biosynthesis in DR and DS rats, it was noted that the PGE response to specific stimuli was dependent on the type of stimulus applied. Rats fed either a 0.3% of 4% NaCl diet from 3 weeks of age were killed at 13 to 15 weeks of age. The renal papilla was sectioned and incubated in Krebs-Henseleit buffer. We stimulated PGE biosynthesis by incubation of tissues in hyperosmolal buffer (1500 mOsm NaCl) or in the presence of furosemide (3 mmol/L). PGE production was determined by radioimmunoassay of the incubation buffer. The PGE biosynthesis in response to hyperosmolality was significantly greater in the groups fed the 4% NaCl diet, independent of rat strain. The PGE biosynthesis in response to furosemide was significantly greater in each group of DR rats, independent of dietary NaCl. These results suggest that in the renal papilla of the Dahl rat stimulation-secretion coupled PGE biosynthesis is dependent not only on genetic determinants but also on the type of stimulus applied.