Aspergillus fumigatus, a ubiquitous fungus, is implicated in the pathogenesis of a number of clinically different allergic diseases in man. Peptide-based immunotherapy may offer an alternative in patient care and management. The purpose of this study was to evaluate the role of T cell epitopes of A. fumigatus ribotoxin, Asp f 1 in inducing tolerance in mice exposed to A. fumigatus antigen. The epitope analysis in BALB/c mice using synthetic peptides of Asp f 1 demonstrated both cryptic and dominant epitopes detected from 42 through 54 and 155 through 167 aa, accordingly. Intravenous injection of these peptides markedly inhibited the response induced by the exposure to crude A. fumigatus extract in mice as evidenced by the in vitro interleukin-2 (IL-2) production and proliferation of T-lymphocytes. Cytokine transcription studies indicate that, when stimulated with the peptides in immunogenic conditions, the major peptide (aa 155-167) specific T cell clone produced only IFN-gamma, but not IL-4. The ability of both dominant and cryptic peptide epitopes of a single molecule to induce tolerance against the immune response to a multi-molecular allergen complex has significant implication for peptide-based immunotherapy.