We have previously noted that bile duct ligation (BDL) in the rat results in decreased creatinine clearance (Ccr) and decreased urinary sodium excretion (UNaV) as well as increased renal prostaglandin (PG) production. This study was undertaken to assess the role of increased renal PG production in the change in renal function after BDL and to determine if these changes are mediated by the renin-angiotensin system. After baseline measurement of renal function, Sprague-Dawley rats underwent either sham operation (SO) or BDL. Four days later animals received a single intraperitoneal injection of either 0.9% saline, 0.5 ml/kg (SO, n = 10; BDL, n = 10), or indomethacin, 5 mg/kg (SO + Indo, n = 10; BDL + Indo, n = 10), and renal function was reassessed. Plasma renin activity was measured at the end of the second study period. BDL resulted in a 40% decrease in Ccr (p = 0.000), a 38% decrease in UNaV (p = 0.002), a twofold increase in urinary 6-keto-PGF1 alpha excretion (p = 0.005), and fourfold increases in urinary excretion of PGE2 (p = 0.006) and thromboxane B2 (p = 0.000). Indomethacin prevented the increase in urinary PG excretion otherwise seen with BDL and resulted in an additional 41% reduction in UNaV (p = 0.018). Further reductions in Ccr by indomethacin, however, were minimal and nonsignificant. Plasma renin activity did not differ among any of the groups. These findings indicate that the sodium retention associated with BDL is attenuated by the concomitant rise in renal PG production. This elevation in PG production, however, does not protect against the adverse effects of BDL on Ccr. Furthermore, the changes in renal function that occur after BDL do not appear to be mediated by the renin-angiotensin system.