Th1 cells play a critical role in the induction of cell-mediated immune responses and eradication of intracellular pathogen. The dose and route of immunization of antigen are also determining factors. It remains unclear what types of immunogenic peptide can induce the Th1 development and how it acts to regulate the immune system. Ag85B (also known as alpha antigen or MPT59) has been shown to be the most potent antigen species yet purified in humans and in mice. Strong Th1 responses have been elicited in vitro from PPD(+) asymptomatic individuals and Ag85B-primed cells of C57BL/6 (I-A(b)) mice. Peptide-25 (aa240-254) of Ag85B is a major Th1 cell epitope in I-A(b) mice. Active immunization of C57BL/6 mice with Peptide-25 can induce the development of CDT4(+) TCRVbeta11(+) and CDT4(+) TCRVbeta11(-)Th1 cells that produce IFN-gamma- and TNF-alpha, and protects against subsequent infection with live Mycobacterium tuberculosis H37Rv IFN-gamma. Peptide-25 has a potent adjuvant activity in both humoral and cell-mediated immune responses that is mediated by Th1 cells. We would propose to designate Peptide-25 as "Th1-inducing peptide".