BACKGROUND AND OBJECTIVE: The induction of allergic sensitization is the key process of guinea pig asthma model, but few studies has been done on allergen sensitization per se. We performed to investigate the effect of initial sensitization route on asthmatic reactions in response to subsequent repeated allergen challenges. Subjects and METHODS: Thirteen guinea pigs were sensitized with ovalbumin by intraperitoneal injection(group A) and 14 by exposure to aerosolized ovalbumin(group B) on two occasions separated by 1 week. Animals were challenged by inhalation of stepwise increasing concentration of 0.1, 0.5, 1, and 2% ovalbumin every 2 weeks 5 times. We used Penh (enhanced pause) as an index of airway constriction. Allergen inhalation discontinued when an increase of Penh more than 200%, and provocative concentration of ovalbumin causing a 200% increase in Penh was defined as PC200 Bronchoalveolar lavage and histopathological examination of lung tissue was done 24 after last challenge. RESULTS: On first challenge, 11 (85%) of group A had asthmatic reactions, but only 5 (36%) of group B did. Geographic mean of PC200 was significantly lower in group A than that of group B(0.26% vs. 1.26 %, p<0.01). On repeated allergen challenge, PC200 of group A was relatively unchanged, but that of group B was much variable. Sensitized guinea pig had increased eosinophil infiltration in BAL and there are no differences between group A and B in lang pathology. CONCLUSION: Ovalbumin sensitization by intraperitoneal injection of guinea pig is better than inhalation method in first allergen challenge and unvaried asthmatic reactions on repeated challenges.