The expression of the human mu opioid receptor splice variants (hMOR-1A, hMOR-1O, hMOR-1X, and hMOR-1Y) mRNA in peripheral blood lymphocytes (PBLs) was explored in opioid addicted, methadone maintained, long-term abstinent, and control subjects. Real-time PCR showed that hMOR-1X and hMOR-1Y are not expressed in PBLs. The hMOR-1A mRNA was 0.33 fold down-regulated in abstinent and 1.94 fold up-regulated in methadone maintained subjects. The hMOR-1O mRNA was down-regulated 0.39 and 0.53 fold in abstinent and methadone maintained groups, respectively. Expression of both variants in addicted group was not different from controls. It is concluded that expression of hMOR-1A and hMOR-1O variants measured by a suggested peripheral marker can serve to identify people at risk for opioid addiction and also to evaluate the successfulness of methadone therapy.