During the study of the pathological significance of circulating endothelin (ET) in acute renal failure (ARF) we measured ET in 7 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 (mean age 11.1+/- 6.3 years) 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 than in the recovery period, but comparing to plasma ET in the healthy children, the difference was only on borderline statistical significance. 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 glomerular filtration (GFR) was not the main factor determining the increased ET in ARF. We suggest that elevated plasma ET in ARF may be secondary to vascular endothelial dysfunction and speculate that engancement synthesis of endothelial relaxing factor (EDRF) inhibits ET synthesis during the recovery period. The pathogenetic role of circulating ET in ARF cannot be determined from the present study.