Objective: This study was conducted to examine the effects of endothelin (ET)-1 and ET-3 on hepatic venules and sinusoids and to identify the subtypes of ET receptors. Method: Hepatic venules and sinusoids of anesthetized mice were observed at the edge of the liver. ET-1, ET-3 and sarafotoxin (S6c, a selective ETB receptor agonist) were applied topically over the microvasculature. Results: ET-1, ET-3 and S6c (1-100 µM, 30 µl) induced dose-dependent vasoconstriction of the portal venules, the sinusoids and the central venules. The ETs and S6c were equipotent for these microvessels. BQ-123 (a selective ETA receptor antagonist) inhibited the constrictive effects of ET-3 (not of ET-1) on the portal venules and central venules, whereas it had no inhibitory effect on the sinusoids. Conclusions: In mouse hepatic venules and sinusoids, the vasoconstriction induced by ET-1 and ET-3 was mediated mainly through the ETB receptor subtype and partly through an unknown BQ-123-sensitive ET receptor subtype in the portal and central venules, and only through the ETB receptor subtype in the sinusoid