Endothelin is the most potent vasoconstrictor peptide known today. Using a radioimmunoassay for endothelin, we measured immunoreactive endothelin in culture media of guinea pig sinusoidal endothelial liver cells and human umbilical vein endothelial cells. A time-dependent release of immunoreactive endothelin by confluent sinusoidal endothelial liver cells in culture was found. Sinusoidal endothelial liver cells produced similar amounts of immunoreactive endothelin as umbilical vein endothelial cells, about 900 pg/microgram DNA per 24 h. In the presence of transforming growth factor beta a dose-dependent increase of immunoreactive endothelin release was measured. The maximal increase of 50% was found at a concentration of 1 ng transforming growth factor per ml. To a similar extent Kupffer cell-conditioned media augmented the release of immunoreactive endothelin by sinusoidal endothelial liver cells, especially when Kupffer cells had been stimulated by endotoxin. Endotoxin itself did not alter the release of immunoreactive endothelin. Endothelin released by sinusoidal endothelial liver cells might influence the pericytes of the liver, i.e., the Ito-cells.