Isolated kidneys of Dahl salt-sensitive rats (DS) excrete sodium less readily than those of Dahl salt-resistant rats (DR). The collecting tubule is an important source of papillary prostaglandin E2and is a site of significant sodium reabsorption. We cultured renal papillary collecting tubule cells from 5-week-old, prehypertensive DS and DR on a low salt diet and also after 14 weeks of high salt feeding, and we measured prostaglandin E2synthetic capacity. Unstimulated renal papillary collecting tubule cells from 5-week-old DS produced 62 ± 5% less prostaglandin E2than did comparable cells from DR (p< 0.001). The cells from DS also synthesized less prostaglandin E? after stimulation with the calcium ionophore A23187 (67 ± 6% of control; p < 0.001) or the addition of exogenous arachidonate (74 ± 7% of control;p< 0.01). Urinary prostaglandin E? excretion was also diminished in the 5-week-old DS compared with their salt-resistant counterparts (18.1 ± 1.3 vs 23.9 ± 1.7 ng/24 hr;p< 0.025). After high salt feeding, the DS became hypertensive but the DR remained normotensive. Renal papillary collecting tubule cells cultured from these DS continued to produce less prostaglandin E2than those from control rats, both in the basal state (60 ± 12% of control;p< 0.09) and after stimulation with ionophore (62 ± 2% of control;p< 0.002). In these older animals, the DS continued to underexcrete prostaglandin E? compared with the DR (29.7 ± 3.2 vs 42.2 ± 6.1 ng/24 hr;p< 0.08). The underproduction of prostaglandin E2in the papillary collecting tubule of DS may play a role in their inadequate renal natriuretic capacity and contribute to the onset and maintenance of saltinduced hypertension in this strain.