The alteration of peripheral blood T-and B-lymphocyte proliferative responses were determined during different periods of withdrawal in heroin (Hw) and heroin / bhang (HBw) addicts. The results clearly demonstrated a significant decrease in the response of T- lymphocytes to PHA-stimulation and secretion of IL-2 in both Hw and HBw addicts. The in vitro presence of naloxone induced further inhibition of the PHA proliferative response and IL-2 production. Our data also indicated a significant suppression of IFN-gamma levels by human blood lymphocytes from Hw and HBw addicts. Additionally, a significant suppression of IFN-gamma production was demonstrated in the presence of naloxone. Moreover, IL-4 production was suppressed in Hw, but not in HBw groups and the in vitro presence of naloxone did not affect the level of IL-4 in both groups. However, IL-10 production was significantly increased in both groups accompanied by a significant suppression of IL-10 secretion in the presence of naloxone. In contrast, IL-5 levels stimulated by PHA showed a significant increase in both groups, while no significant effect of naloxone could be observed. Our results suggested that heroin administration can cause measurable suppression of some components of the human cellular immune system. The results further demonstrated that the immunsuppressive effect observed after heroin use are naloxone-mediated and suggested that activation of the adrenal gland is one potential mechanism for this effect.