Naloxone, 0.3 mg/kg of a 10 mg/ml solution, was administered as a single bolus to patients in septic shock if their systolic blood pressure (BP) was less than 100 mm Hg or MAP less than 70 mm Hg with evidence of renal or cerebral hypoperfusion. Patients with chronic or acute (less than 12 h) administration of narcotics were excluded. Ten patients received naloxone; 5 patients had significant increases in blood pressure; 5 had no response. Maximal response in BP occurred by 15 min, and lasted 45-165 min. Responders could not be separated by nonresponders by analysis of baseline, hemodynamics, or prior steroid therapy; nonresponders were hemodynamically compromised greater than 24 h; responders less than or equal to 8. Two patients in each group were chronically on high-dose steroids and responded to a 2nd smaller dose of naloxone when effects of initial bolus had ended. Naloxone, 0.3 mg/kg, can reverse endorphin-mediated hypotension in acute septic shock in patients who have received chronic steroid therapy.