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 <100 mm Hg or MAP <70 mm Hg with evidence of renal or cerebral hypoperfusion. Patients with chronic or acute (24 h; responders ≤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.