Endothelin is a recently described, potent renal vascular and systemic vasoconstrictor peptide. To evaluate the response of this peptide to volume contraction, we measured eight baseline and posthemodialysis samples from seven children, aged 14.5 ± 3 years, with chronic renal failure. Plasma was extracted and endothelin-1 was measured by radioimmunoassay. Dialysis was performed for a 3- to 3½-hour period, and body weight decreased from 38.0 ± 14.3 to 36.2 ± 13.8 kg (p <0.01) during this time. There were no significant changes in heart rate or respiratory rate after dialysis, but blood pressure fell from 127/80 ± 22/16 to 114/72 ± 20/21 mm Hg (p = 0.05 for the systolic pressure). Plasma endothelin-1 concentration increased from 1.5 ± 1.2 pg/ml at baseline to 7.3 ± 8.9 pg/ml (p = 0.06) after dialysis; the fall in body weight from dialysis correlated with the increase in endothelin (r = −0.75; p = 0.05). Thus volume contraction from hemodialysis is associated with a rise in plasma endothelin-1, which is related to the acute change In body weight.