Rationale: Despite accumulating evidence that psychological stress has a short-lasting detrimental effect on asthma, little is known about the way stress in childhood predisposes adult asthma. Objectives: Using a communication box, we investigated the long-lasting effect of early psychological and physical stress on adult asthma in mice. Methods: Male Balb/c mice were exposed to either psychological stress or physical stress three times (every other day) during their fourth week of life. The mice were sensitized to ovalbumin at eight and ten weeks, and an ovalbumin airway challenge was conducted at the age of 11 weeks. Results: 24 hours after the ovalbumin challenge, both psychological and physical stress-exposed mice exhibited a significant acceleration in the number of total mononuclear cells and eosinophils and airway hyperresponsiveness compared with control mice. No differences of the serum anti-OVA-specific immunoglobulin E levels were found between stress-exposed and control animals after antigen sensitization. In the psychological stress group, but not in the physical stress group, an elevation of the serum corticosterone levels during ovalbumin challenge was significantly attenuated in comparison with the control group. Moreover, pre-treatment with RU-486, a glucocorticoid receptor antagonist, before ovalbumin challenge completely inhibited a psychological stress-induced exacerbation of asthma. However, pre treatment with GR-82334, a neurokinin-1 receptor antagonist, failed to affect physical stress-induced augmentation of airway inflammation. Conclusion: Early psychological and physical stresses aggravated adult asthma via hypothalamic-pituitary-adrenal axis hyporesponsiveness during antigen challenge and via a pathway(s) distinct from the hypothalamic-pituitary-adrenal axis or neurokinin-1 receptors.