Increasingly in recent years, thyroid hormones (THs) have been considered to be important regulators of the immune system. However, their roles in host defense against viral infections are not clearly established. Therefore, this study was undertaken to examine proliferative activity and cytokine production by lymphocytes isolated from hyperthyroid and euthyroid Balb/c mice in response to herpes simplex virus-1 (HSV-1). Lymphocytes of hyperthyroid animals showed a significantly higher rate of proliferation and interferon (IFN)-γ production when compared with that by lymphocytes from euthyroid mice. In vitro thyroxine (T4) treatment was similarly effective in the potentiation of proliferation, but not IFNγ production, by euthyroid lymphocytes. Furthermore, the hyperthyroid state significantly attenuated ConA-, but not HSV-1-, induced interleukin (IL)-10 release; in vitro T4 treatment synergized this effect. These findings suggest that supra-physiologic TH levels (i.e. as occur in hyper-thyroid states) or in vitro TH treatment modulate T-helper (TH)1/TH2 lymphocyte responses and thereby amplifies host defenses against viral infections. One may also conclude that THs may have a potential application in viral immunization and/or treatment of viral infections.