Supplementation with both cystine and glutamic acid increases the synthesis of glutathione (GSH), which has a marked effect on immune cell function, as compared with supplementation with either amino acid alone in human macrophages in vitro. As dietary glutamic acid is metabolized during intestinal transport, oral administration of _L-theanine (γ-glutamylethylamide), which is metabolized to glutamic acid mainly in the liver, may act as a glutamic acid donor in vivo. The present study was performed to investigate the effects of oral administration of _L-cystine and/or _L-theanine on GSH levels and immune responses. Co-administration of _L-cystine (200 mg/kg) and _L-theanine (80 mg/kg) for 11 days before immunization significantly increased the levels of total GSH in the liver 6 hr after immunization as compared with the levels in control mice. To examine the effects of administration of _L-cystine and/or _L-theanine on the balance of T helper (Th) 1/Th2 cell responses, the serum ratios of the Th1 cytokine, interferon (IFN)-γ, and the Th2 cytokine, interleukin (IL)-10, were investigated. At 24 hr after immunization, co-administration significantly increased the IL-10/IFN-γ ratio compared with the ratios of the control and single-administration mice. Furthermore, co-administration before primary immunization significantly enhanced serum antigen-specific IgG levels. Taken together, these findings suggest that co-administration of _L-cystine and _L-theanine enhances antigen-specific IgG production partly through augmentation of GSH levels and Th2-mediated responses.