A marked increase in immunoreactive endothelin was observed in rat serum collected within 10-15 min after infusion of endotoxin. Endothelin level was 117 +/- 11.5 pg/ml (mean +/- S.E., N = 4) in rats exposed to endotoxin as compared with undetectable levels (less than 2 pg/ml, N = 4) in controls. We have also observed a significant stimulation of endothelin-release by endotoxin from cultured bovine transformed thoractic aortic endothelial cells at concentrations of endotoxin ranging between 0.1 and 10.0 micrograms/ml. Serum was indispensable for the stimulating effect of endotoxin, although serum itself did not show any effect at the concentration used (1%). These results suggest that endothelin plays an important role in mediation of pathophysiological responses caused by endotoxin. The levels of endothelin were measured by radioimmunoassay with high sensitivity.