The study was carried out to determine the urinary excretion of endothelin-1 (ET-1) in normal pregnancy and to define its possible role in mediating the renal response to aldosterone and arginine vasopressin (AVP). Measurements were performed in 12 healthy pregnant women serially in the 20th, 24th, 28th, 32nd and 36th weeks of pregnancy. Urinary ET-1, plasma and urinary aldosterone and AVP levels (RIA methods) as well as plasma and urine sodium, potassium, creatinine and osmolality were measured; creatinine clearance (Ccr), osmolar clearance (Cosm) and free water clearance (CH2O) calculated. Fractional sodium excretion (FENa), urine sodium/potassium ratio (Na/K) and transtubular potassium concentration gradient (TTKG) were also determined. It was demonstrated that urinary ET-1 excretion was higher in pregnant than in non-pregnant women and it increased further as the pregnancy progressed from 34.8 +/- 4.0 pmol/day in week 20 to 44.1 +/- 3.2 pmol/day in week 36 (P < 0.01). Daily ET-1 excretion significantly correlated with AVP (r = 0.39, P < 0.005) and aldosterone excretion (r = 0.62, P < 0.0001). Furthermore, there was a significant positive relationship between ET-1 excretion and urine flow rate (r = 0.67, P < 0.0001), CCR (r = 0.40, P < 0.0025), Cosm (r = 0.58, P < 0.001), sodium (r = 0.56, P < 0.001) and potassium excretion (r = 0.42, P < 0.001). However, such a relationship could not be established between ET-1 excretion and FENa, TTKG and Na/K.(ABSTRACT TRUNCATED AT 250 WORDS)