To study the pathological significance of circulating endothelin (ET) in ARF, we measured plasma ET in seven children (mean age 8.8 +/- 4.4 years) with ARF in the most severe phase and 3.7 +/- 3.5 months later in the recovery period. Twenty-seven healthy children were included in the study as controls. Plasma ET level was measured by highly sensitive and specific radioimmunoassay for ET-1 and ET-2 (ET-1/2, Biomedica, Vienna). Plasma ET was significantly higher in the most severe phase of ARF (4.75 +/- 4.08 fM/ml) than in the recovery period (0.78 +/- 0.24 fM/ml; p < 0.01), but comparing to plasma ET in the healthy children, the difference was only of borderline statistical significance (Pf, 0.0573). Since plasma concentrations of creatinine did not correlate with plasma ET in patients, either in acute or in the recovery phase of disease, we concluded that decreased GFR is not the main factor determining an increased ET in ARF. We suggest that elevated plasma ET in ARF may be secondary to vascular endothelial dysfunction and speculate that enhancement synthesis of endothelial relaxing factor (EDRF) inhibits ET synthesis during the recovery period. We did not find any relationship between plasma ET and blood pressure (BP) in patients with ARF, so we conclude that circulating ET is not the main factor determining BP in ARF.