We investigated the effect of different concentrations of morphine and tramadol on the differentiation of human adult helper T cells in vitro. Twenty outpatients without any immune diseases were selected and their peripheral blood was collected. Whole blood or peripheral blood mononuclear cells (PBMCs) were pretreated with different concentrations of morphine or tramadol for 48 h, while the control group received neither. The ratio of CD4+IFN-g+IL-2+=CD4+IL-4+IL-10+ was analysed by three-color flow cytometry.1 The intracellular cytokines, after stimulation with PMA and Ionomycin (Ion), were detected by trace whole blood technology. The CD4+CCR5+ and CD4+ CCR3+ cells in PBMCs were counted in order to observe the imbalance of Th1=Th2. After treatment with morphine or tramadol, the number of Th2 increased significantly and the ratio of Th1=Th2 decreased dramatically in both groups. At the same time the number of CD4+IFN-g+ IL-2+ cells decreased and CD4+IL-4+IL-10+ cells increased sharply as compared with the control group. Both morphine and tramadol can direct Th0 cells toward Th2, especially morphine. The Th2 redirection, as well as the changes in cytokines, showed a dose dependent fashion in both drugs