The present study was carried out to determine the response of urinary ET-1 excretion to furosemide administration in human neonates. Ten newborn infants with mean birthweight of 2752 g and mean gestational age of 37.1 weeks were given furosemide in a dose of 1 mg/kg. Prior to anc following furosemide therapy urine was collected for a period of 12 hr and analyzed for creatinine, osmolality, sodium and potassium as well as for AVP, aldosterone and ET-1. Inresponse to furosemide administration urine flow rate and urinary osmolar, sodium and potassium excretion increased significantly, whereas creatinine excretion remained unchanged. Furthemore, following furosemide therapy there was an increase in AVP (19,5±5.4 vs 28.7±7.8 pg/kg/hr, p=0.06, NS), aldosterone (507±12o vs 751-203 ng/kg/hr, p<0.05) and ET-1 (36.0±5,6 vs 61.4±8.7 fmol/ kg/hr, p<0.05) excretion, respectively. Urinary ET-1 excretion was found to correlate positively with diuresis (r=0.75, p<0.001), sodium (r=0,53, p<0,0025), osmolar (r=0,73, p<0.001)and AVP excretion (r=0,72, p<0.001)but not with aldosterone excretion (r=0.10, p=0.96) It is concluded that the furosemide-induced diuresis and natriuresis is associated with significantly increased urinary ET-1 excretion which may further inhibit sodium and water reabsorption in the distal nephron. The enhanced generation of ET-1 in the renal medulla appears to be related to decreased medullary tonicity and AVP stimulation.