Organic acid anhydrides (OAAs) are industrial chemicals that may cause induction of specific IgE and airway symptoms in exposed workers. They are a good model for studies of relationships between chemical structure and the sensitizing potential of reactive low-molecular-weight compounds. Hexahydrophthalic anhydride (HHPA) is such a compound. This study aimed to evaluate the relationship between specific IgG1 levels and airway responses in a model to predict the sensitizing potential of OAAs. Guinea pigs were either actively or passively sensitized to HHPA. For active sensitization, guinea pigs were injected i.d. with 0.1 ml of olive oil (vehicle) or 0.05, 0.5, or 5% HHPA in olive oil. Passive sensitization was performed by i.p. injection of different volumes of antisera (0.75-6 ml, either unheated to keep IgE or heated to destroy IgE) taken from HHPA-sensitized guinea pigs. Specific antibody levels were evaluated with ELISA and passive cutaneous anaphylaxis. Animals were challenged 16-18 days after active sensitization, or 2 days after passive sensitization, by intratracheal instillation with HHPA conjugated to guinea pig serum albumin (HHPA-GPSA; 0.05% in saline), and the immediate effects on lung resistance (RL), and plasma extravasation, measured as Evans blue dye extravasation, for up to 6 min were recorded. Active sensitization caused production of specific IgG1. Provocation with HHPA-GPSA caused an increase of both RL and Evans blue dye extravasation, which was dependent upon the active sensitization dose. Challenge with HHPA-GPSA in passively sensitized guinea pigs also produced an increase in both RL and Evans blue dye extravasation which was related to the IgG1 level. In the guinea pig model of HHPA-induced airway allergy, the airway responses are closely related to the serum levels of specific IgG1. Thus, the IgG1 levels induced by the immunization may reflect the sensitizing potential of HHPA.