Opiate addiction influences many physiological functions including immune responses. The objective of this study was to investigate the immune system function in heroin addicted patients submitted to methadone or buprenorphine maintenance treatment compared to untreated heroin addicts and healthy controls. Four groups were studied: group A included nine heroin addicted subjects, who were still injecting heroin; groups B and C were composed of 12 patients previously addicted to heroin, being treated with methadone (mean dosage 58+/-12.7 mg/day) or buprenorphine (mean dose 9.3+/-2.3mg/day) since at least 6 months; group D was composed of 15 sex and age matched healthy controls. Lymphoproliferation and peripheral mononuclear cell cultures production of the Th1 cytokines IL-2 and IFN-gamma, the Th2 cytokine IL-4, and of the pro-inflammatory cytokine TNF-alpha were evaluated in all the patients and controls. PHA-lymphoproliferation was lower in untreated heroin addicts than in controls, while it was normal in methadone and buprenorphine treated patients. An altered Th1/Th2 balance, characterized by reduced IL-4, IFN-gamma and TNF-alpha but normal IL-2 levels, was present in untreated heroin addicted subjects, while the Th1/Th2 balance was well conserved in the methadone and buprenorphine groups. These findings suggest that the immune system abnormalities in heroin addicted patients can be restored to almost normal values by controlled treatment with methadone and buprenorphine.