Treatment of septic shock with naloxone was evaluated in a prospective, randomised, double-blind, placebo-controlled study in which ten episodes of shock were treated with naloxone (0.4 to 1.2 mg intravenously) and 13 with the vehicle for injection. Treatment groups were similar in terms of demographic characteristics, type of primary infection, prevalence of septicaemia, type of underlying disease, duration in shock, and vasopressor therapy. Mean systolic blood pressure rose by 13.3% in the naloxone group and 11.3% in the placebo group. Two-way analysis of variance for repeated measures of blood pressure, obtained over 30 min periods before and after treatment, revealed no significant difference (p greater than 0.10) between treatment groups. Survival rates in the two groups at 48 h and 7 days after the start of treatment were similar. Naloxone, 0.4 to 1.2 mg intravenously, was no better than placebo in ameliorating hypotension in septic shock.