To investigate mechanisms underlying allergen-induced asthmatic reactions, airway hyperresponsiveness and remodeling, we have developed a guinea pig model of acute and chronic asthma using unanesthetized, unrestrained animals. To measure airway function, ovalbumin (IgE)-sensitized animals are permanently instrumented with a balloon-catheter, which is implanted inside the pleural cavity and exposed at the neck of the animal. Via an external cannula, the balloon-catheter is connected to a pressure transducer, an amplifier, an A/D converter and a computer system, enabling on-line measurement of pleural pressure (P_pl)—closely correlating with airway resistance—for prolonged periods of time. Using aerosol inhalations, the method has been successfully applied to measure ovalbumin-induced early and late asthmatic reactions and airway hyperresponsiveness. Because airway function can be monitored repeatedly, intra-individual comparisons of airway responses (e.g., to study drug effects) are feasible. Moreover, this model is suitable to investigate chronic asthma and airway remodeling, which occurs after repeated allergen challenges. The protocol for establishing this model takes about 4 weeks.