Plasma immunoreactive endothelin-1 concentrations were determined by radioimmunoassay in 11 septic patients during the first 24 hours after the development of the sepsis syndrome in 15 nonseptic postoperative patients studied 24 hours after open heart surgery and in 14 healthy volunteers. Mean endothelin-1 plasma concentrations were significantly (p < 0.001) increased in septic patients (19.9 ± 2.2 pg/mL, mean ± standard error) compared to concentrations found in postoperative cardiac patients (11.9 ± 0.7 pg/mL) or in healthy volunteers (6.1 ± 0.3 pg/mL). In septic patients elevated plasma concentrations of endothelin-1 were inversely correlated with cardiac index (r = -0.80, p < 0.005) and positively correlated the severity of illness as documented by APACHE II score (r = 0.74, p < 0.01) and plasma creatinine levels (r = 0.80, p < 0.005). No such correlations were found in postoperative cardiac patients. These results indicate that endothelin-1 concentrations are correlated with the severity of illness and depression of cardiac output in patients with sepsis.