The authors conducted a double-blind placebo-controlled study in which patients with a wide range of manic symptoms were administered 20 mg of naloxone subcutaneously. Naloxone failed to improve manic severity, activation-arousal, or elation-grandiosity for intervals up to 3 hours. Global nurse ratings of mania did not improve over an 8-hour period. The authors suggest that the question of endorphin involvement in mania has not been resolved and recommend clinical studies with longer acting oral narcotic antagonists such as naltrexone.