Plasma levels of immunoreactive endothelin (ir-ET) at basal resting conditions and the effects of indomethacin (150 mg orally) on the plasma level of ir-ET and renal haemodynamics were evaluated in 14 healthy uninephrectomized subjects (Unx) and in 14 sex- and age-matched healthy controls subjects (Cs). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion clearance technique using 125iothalamate and 131I-hippuran as references substances. Immunoreactive endothelin was measured by radioimmunoassay after prior extraction. At basal resting conditions the plasma level of ir-ET was significantly higher in the Unx group. (Unx: 1.28 pmol/l versus Cs: 0.99 pmol/l, P = 0.02, medians). After indomethacin the plasma level of ir-ET increased significantly in both groups and the ir-ET level remained significantly higher in the Unx group compared with the Cs group. Both GFR and RPF decreased significantly after indomethacin (after 120 min: Unx: GFR, -10.9%; RPF, -6.7%; and Cs: GFR, -12.5%; RPF, -7.8%, medians). A negative correlation in the percentage decrease in GFR (rho = -0.58, P = 0.03) and RPF (rho = -0.61, P = 0.03) and the percentage increase in ir-ET 2 h after indomethacin was only found in the Cs group. It is concluded that healthy uninephrectomized subjects have a higher level of ir-ET than healthy controls subjects both during basal conditions and after indomethacin. Indomethacin ingestion resulted in comparable decreases in renal haemodynamics in the two groups. It is suggested that the enhanced ir-ET in uninephrectomized subjects could be due to an abnormal renal metabolism of endothelin in the remnant kidney.