Six atopic subjects with grass pollen allergy and six nonallergic healthy volunteers were enrolled into this study. Substance P-like immunoreactivity (SP-LIR) and beta-endorphin-like immunoreactivity (beta E-LIR) were determined in bronchoalveolar lavage (BAL) and nasal lavage (NAL) fluids before and after allergen (grass pollen) provocation. A significant increase in the baseline concentration of SP-LIR and beta E-LIR was seen in BAL of allergic subjects. In NAL of allergic subjects an increased baseline concentration of SP-LIR was found (beta E-LIR not detectable). After allergen provocation there was a rise of SP-LIR and beta E-LIR in BAL fluids of allergic subjects immediately after provocation. In NAL fluids of allergic subjects allergen challenge resulted in a rise of SP-LIR within 10 minutes. Allergen provocation did not influence SP-LIR and beta E-LIR concentration in BAL and NAL in nonallergic controls. The demonstrated higher baseline levels of SP-LIR and beta E-LIR as well as the increase after provocation in the BAL and NAL of allergic subjects but not in nonallergic controls support the hypothesis that these neuropeptides contribute to allergic reactions in airways of humans.