Rationale Epidemiological studies have shown an inverse relationship between exposure to antigens early in life and development of allergy and asthma. Exposure to allergen in the first week of life may stimulate active immune tolerance to subsequent stimulus. We hypothesized that neonatal exposure to specific allergen (OVA) or endotoxin, a powerful immunomodulator, in the upper airway of mice would prevent asthma development in the adult. Methods Newborn (5 days after birth) non-anesthetized BALB/C mice received repeated intranasal (IN) application (exposure) of 5 microlitres 1%OVA, or 0.5 ug of endotoxin LPS in each nostril. At 6 weeks of age, the mice received repeated IN application (sensitization) of 1%OVA, 5 microliters in each nostril and were then challenged, 2 weeks later, with IN OVA for 5 days Results In this study we examined changes in airway responsiveness to methacholine as a physiologic measure of lower airway allergic responses. Results show significant decrease in airway hyperresponsiveness to MCH in mice who received OVA or LPS in the neonatal period compared with controls ( P<0.05). OVA-specific serum IgE and frequency of inflammatory cells in BAL fluid were also significantly reduced in these neonatally exposed animals. Conclusions Allergen specific tolerance can be induced by neonatal exposure to same antigen (OVA) or the powerful immunomodulator LPS. Early exposure can abrogate the development of AR and asthma in the adult.