Endothelin-l is a novel endothelium-derived vasoconstrictive peptide. Using a highly specific and sensitive radioimmunoassay for endothelin-l, plasma levels of immunoreactive endothelin- I were measured in 32 research subjects with normal renal function (21 normal subjects and II patients with essential hypertension), 24 patients with nondialyzed chronic renal failure, and 51 patients undergoing maintenance hemodialysis. Although there was no significant difference in plasma immunoreactive endothelin-l levels among the three groups, patients with essential hypertension had significantly higher plasma endothelin-l levels than normal subjects (2.29±1.09 vs. 1.41±0.50 pg/ml, p<0.025). When nondialyzed and hemodialyzed patients were divided into hypertensive and normotensive groups, the nondialyzed hypertensive group (n=17) had higher plasma endothelin-l levels than the comparable normotensive group (n=7) (3.08±3.43 vs. 0.73±0.34 pg/ml, p<0.05), and the hemodialyzed hypertensive group (n=18) had higher plasma endothelin-l levels than the comparable normotensive group (n=33) (2.66±1.92 vs. 1.35±0.73 pg/ml, p<0.005). Plasma atrial natriuretic factor, arginine vasopressin, renin activity, and aldosterone concentration did not show significant differences between hypertensive and normotensive individuals or a correlation with plasma endothelin-l levels. These data suggest that circulating endothelin-l may be partly involved in the development or maintenance of hypertension in humans.