The aim of the present study was twofold: first, to investigate in sheep subjected to endotoxin-induced lung injury whether a relationship exists between the plasma concentration of ET-1 and characteristics of ALI such as the increases in lung microvascular pressure and extravascular lung water content, with or without tezosentan; and second, to assess the effects of tezosentan on the activation of PKC-α in lung tissue in parallel with changes in the plasma concentrations of TNF-α and IL-8. Here, CXCL8 is linked to acute respiratory distress syndrome.