The aim of the study was to investigate the release of endothelin-1 (ET-1) in normal and varicose saphenous veins at baseline and after venous stasis test. Ten patients (eight women and two men, mean age 43 +/- 4) with primarily varicose great saphenous veins and ten controls (eight women and two men, mean age 42 +/- 6) were recruited. After 30 minutes of resting in supine position, venous occlusion in a leg was performed with a sphygmomanometer provided to keep the pressure in the cuff intermediate between systolic and diastolic blood pressure for 10 minutes. Blood samples were taken from the great saphenous vein just above the medial malleolus at baseline and 10 minutes after venous stasis was begun. Plasma ET-1 was determined by a radioimmunoassay system. Results are expressed as mean +/- SD. Plasma ET-1 concentration was higher in varicose than in normal saphenous veins (4 +/- 0.1 pmol/L vs 2.6 +/- 0.1 pmol/L, P < 0.001), and it significantly increased (P < 0.001) in both groups after venous stasis when compared with baseline (6.8 +/- 0.9 pmol/L and 3.6 +/- 0.1 pmol/L in varicose and normal saphenous veins, respectively). Absolute increase in plasma ET-1 was significantly greater in varicose than in normal saphenous veins (2.8 +/- 0.9 pmol/L vs 1.0 +/- 0.2 pmol/L, P < 0.01). In conclusion, increased local ET-1 release in varicose saphenous veins could be a marker for venous endothelial activation/damage and/or contribute to promote the morphologic alterations of the varicose vein wall by stimulating smooth muscle cell proliferation. On the other hand, increased ET-1 release could contribute to counterbalancing the varicose venous relaxation and to increasing preload in varicose patients via ET-1-induced venoconstriction.