Background: The intranasal administration of peptides containing T-cell epitopes has been shown to inhibit T-cell and antibody responses of mice injected with allergen, but responses to respiratory sensitization might be regulated differently. Objective: This study was designed to examine the effect of intranasal peptide on antigen-induced lung inflammatory responses and delayed hypersensitivity after sensitization by the respiratory mucosa or without sensitization. Methods: Mice were treated with an intranasal tolerizing regimen of a peptide containing the major T-cell epitope of Der p 1. Delayed hypersensitivity and lung inflammation to challenge with Der p 1 was measured either without further treatment or after sensitization induced by means of the intranasal administration of Der p 1 with a mutated enterotoxin adjuvant. Lung inflammatory responses were examined by means of lavage and histologic section, and delayed hypersensitivity responses were measured on the basis of ear swelling. Results: Delayed hypersensitivity reactions were induced in mice treated with intranasal peptide, and large reactions were found in mice given intranasal peptide and sensitized with intranasal Der p 1 and adjuvant. Mice pretreated with peptide and sensitized with Der p 1 had an increased lymphocytic infiltration after allergen-specific challenge, as measured by means of bronchoalveolar lavage and shown histologically. These hypersensitivity results are in contrast to previous data that show tolerance to injected antigen. Conclusions: Although the intranasal administration of a peptide containing a T-cell epitope markedly inhibits responses to sensitization produced by the injection of allergen, the peptide induces immune responses and increases hypersensitivity to respiratory sensitization. (J Allergy Clin Immunol 2002;110:610-6.)