Allergic asthmatic individuals are often exposed to low-doses of allergen in their everyday life. Extended exposure to allergen has lead to down-regulation of the allergic process in cell systems and in animal models. The aim of this study was to evaluate whether any such inhibitory mechanism of allergic responses can be seen in man in vivo. Patients with mild asthma were repeatedly and double-blindly exposed to 25% of the individual dose of allergen that caused an early (EAR) and late asthmatic reaction (LAR). One day after the low-dose allergen or placebo exposure periods, the same individual was given a high-dose allergen challenge. Sputum and blood were collected for the evaluation of eosinophils. Exposure to repeated low doses of allergen induced increased bronchial methacholine responsiveness 6 h after the final allergen exposure (p=0.018), and an increase in the number of eosinophils in sputum. By contrast, the late asthmatic response after challenge with a high dose of allergen was significantly attenuated by approximately 30% at 24 h after the final low-dose allergen exposure (p = 0.03). In summary, repeated low doses of allergen given directly to the airways, attenuate the high-dose allergen-induced late response, despite enhanced bronchial hyperresponsiveness to methacholine and elevated sputum eosinophils prior to allergen challenge.