Large numbers of reports have shown that thermal injury (TI) causes a wide spectrum of defects in immune response that lead to a high susceptibility to various opportunistic infections. However, it is still a matter of debate whether TI induces Th2 polarization or global impairment in Th1/Th2 response. In this study, TI in a mouse model was induced by exposing shaved dorsal skin to boiling water and cytokine production was analyzed. At day 2 of injury, whole spleen cells and T cells were collected and then stimulated with an anti-CD3 antibody. The levels of cytokine secretion were determined by cytokine ELISA. Production of IFNgamma and IL 4 by whole spleen cells from injured mice were concurrently decreased when compared to those from sham-injured controls. Proportional changes in T, B, and T-subset cells were not accompanied. Using purified T cells devoid of accessory cells (AC), it was shown that those defects resulted primarily from lowered T cell potentials. By using mixed cultures of sham T and TI-AC and vice versa, it was revealed that AC also acted as inhibitor cells in IFNgamma and IL 4 production in less extent. Blockade of glucocorticoid signals rendered the T cells partially resistant to TI-induced inhibition in IFNgamma and but not IL 4 production. These results clearly demonstrate that TI induces overall suppression in Th1 and Th2 response through T cell dysfunction together with the inhibition of AC activity, and that reduction in only IFNgamma but not IL 4, production may be caused, in part, by corticosteroid hormone that is secreted prominently during trauma.