The plasma levels of endothelin-1 and big endothelin-1 were evaluated in blood of rats in the superior and inferior vena cava, in normal posture (synchronous controls), and after 12 days head-down suspension and 1 day recovery in normal posture. In synchronous controls, the mean plasma concentration of endothelin-1 in inferior vena cava or superior vena cava was almost the same (5.89 +/- 0.63 pmol/l and 5.67 +/- 0.64 pmol/l, respectively), whereas the mean plasma concentration of big endothelin-1 was higher (p <0.05) in superior vena cava compared to inferior vena cava (5.49 +/-0.75 pmol/l and 1.39 +/-0.15 pmol/l, respectively). In samples from superior vena cava of head-down suspended rats big endothelin-1 levels were significantly lower (p <0.05) up to day 9 of suspension, compared to non-suspended synchronous controls, whereas endothelin-1 values were higher (p <0.05). Big endothelin-1 concentration was higher (p <0.05) in inferior vena cava compared to non-suspended synchronous controls. The behaviour of endothelin-1 was more complex, endothelin-1 levels were lower (p <0.05) on day 1 of head-down suspension and higher (p <0.05) in samples taken on days 9 and 12. After 1 day recovery endothelin-1 and big endothelin-1 concentrations returned to normal in both superior vena cava and inferior vena cava. These data indicate that the endothelial system involvement for the two venous beds is different and suggest that local rather than systemic evaluation could better explain endothelial involvement and the contribution of different anatomic sites to the biosynthesis, conversion and clearance of the various involved molecules.