The treatment efficacy of beta-interferon (beta-IFN) and Copolymer-1 (COP-1) for multiple sclerosis (MS) is potentially attributable to the immune regulatory properties of the drugs. In this study, we compared the regulatory effects of beta-IFN-1a and COP-1 used individually and in combination on the function of T cells derived from MS patients and healthy controls. The results revealed that the two drugs regulated predominantly CD4+ T cells with distinct properties. COP-1 activated both Th1 and Th2 cells while beta-IFN-1a was generally suppressive for Th1 cells and up-regulated IL-10 production. Furthermore, both drugs seemed to alter the T cell responses to myelin basic protein (MBP), a candidate myelin autoantigen for MS. The most significant finding is that COP-1 and beta-IFN-1a act individually through distinct regulatory properties and interact antagonistically when they are combined. The study has important clinical implications in the planned clinical trials to test treatment efficacy of combination therapy.