An investigation was conducted to determine the role naloxone has on immunocompetence in vivo. Mice (n = 7) injected with sheep red blood cells and treated with naloxone (0.1-10.0 mg/kg) show an enhanced production of total and antigen-specific IgM antibody by splenic lymphocytes compared to control (mock-treated) mice. The response was dose-dependent, with the greatest effect occurring at 0.1 mg/kg naloxone. A naloxone-dose of 0.001 mg/kg was not active. In addition, natural killer activity was enhanced in the naloxone-treated mice compared to the controls. The effects on antigen-specific antibody production and natural killer activity were stereoselective, since (-)-naloxone is active whereas (+)-naloxone was not. These results illustrate the ability of an opioid receptor antagonist administered in vivo to regulate immunocompetence to antigen-specific and antigen-nonspecific immune responses, which may be useful during selective inflammatory processes. © 1992.