Arterial, mixed venous (pulmonary arterial), and peripheral venous norepinephrine and epinephrine levels; hemodynamics; and blood lactate levels were measured in 28 patients with septic shock (16 men and 12 women). During hospital follow-up, 18 patients (64%) died of circulatory failure. There were no significant differences in hemodynamic parameters or initial blood lactate levels between survivors and nonsurvivors. Initial arterial, mixed venous, and peripheral venous norepinephrine levels were elevated above normal in both survivors and nonsurvivors. However, norepinephrine levels at all three sampling sites were significantly higher in nonsurvivors than in survivors. Arterial or mixed venous norepinephrine level was better than peripheral venous norepinephrine level in distinguishing survivors from nonsurvivors. In contrast, the differences in plasma epinephrine levels between survivors and nonsurvivors became significantly different only after 48 hr of follow-up. During 60 degrees head-up tilt, the increase in plasma norepinephrine level was significantly higher in survivors compared to non-survivors, suggesting a differential response in the sympathetic nervous system in the two groups of patients. These data suggest that measurement of arterial or mixed venous plasma norepinephrine levels may be a useful guide for assessing the clinical course of patients in septic shock. Moreover, the differences in the sympathetic nervous system response to a 60 degree tilt may predict a poor outcome in these patients.