The capacity of the immune system to participate in processes primarily considered to be central nervous system (CNS) phenomena has been suggested recently by several studies demonstrating the ability of various immune modifiers to attenuate opiate withdrawal severity. The present study demonstrates that within 2 h after injection, the immune modifier cyclosporine A (CsA) has the ability to attenuate the opiate withdrawal syndrome precipitated by naloxone in morphine-dependent animals. Furthermore, it is demonstrated that this effect of CsA can be adoptively transferred by splenic mononuclear cells from immune-modulated (CsA-treated) donors into morphine-dependent recipients. However, unlike direct injections of CsA, CsA-treated immune components require at least 24 h to achieve their full attenuating effect upon withdrawal severity. Since opiate withdrawal behavior is predominantly a CNS-mediated phenomenon, these observations suggest both direct effects of CsA on the brain as well as the participation of immune components in the opiate withdrawal syndrome. This finding lends further support to the hypothesis that immune components have the ability to modulate central nervous system activities in a neuro-immunologic axis of communication.