Our understanding immune response mechanisms to chemical allergens has been limited. It was partly due to the nature of antigens, recognized by T cells, not being well characterized. In the present study, we examined a hypothesis that a reactive chemical allergen, toluene diisocyanate (TDI), react with autologous proteins, thereby inducing T cell responses to the modified self protein in vivo. TDI-human serum albumin (HSA) conjugates were prepared and the presence of antigenic epitopes on the TDI-HSA conjugate was confirmed by IgE ELISA. We examined proliferative and cytokine production responses in TDI-induced asthma patients using the TDI-HSA conjugate as an antigen. Although proliferative responses of peripheral blood mononuclear cells (PBMCs) were not detected, production of IFN-gamma was observed in both PBMC and T cell lines obtained from some newly-diagnosed patients by ELISA. Mitogen-inducible IL-4 production was also detected in some T cell lines. Results of this study may have two implications. One is that presentation of haptenized-self protein to the immune system may induce activation of T cells. The other is that T cells responding to this modified self protein may play a role in the pathogenesis of the chemical allergen-induced asthma by producing cytokines such as IFN-gamma and possibly IL-4.