BACKGROUND Trimellitic anhydride (TMA) can induce specific IgE and occupational asthma. The significance of dermal exposure to TMA in immunologic sensitization and on subsequent airway responses is not clearly known. An animal model displaying both an early-phase airway response (EAR) and a late-phase airway response (LAR) after sensitization and subsequent inhalation challenge to a low-molecular-weight chemical has not been previously reported. OBJECTIVE The present study investigated EAR and LAR after TMA inhalation challenge in Brown Norway rats sensitized by skin exposure to TMA dry powder. METHODS Twenty milligrams of dry TMA powder was applied to the skin of each clipped rat's dorsum on days 0, 7, 14, and 21 and occluded overnight with surgical tape. Rats were challenged for 10 minutes with 0.2 to 40 mg/m(3) of TMA aerosol after day 35. Enhanced pause (an index of airway resistance) was recorded overnight in a whole-body plethysmography system. Specific IgE and pulmonary eosinophilia were also measured. RESULTS Concentration-dependent responses to TMA were observed: provocation with 0.2 mg/m(3) produced no response; 1 mg/m(3) induced only EAR; and 5 mg/m(3) and 40 mg/m(3) induced both EAR and LAR. Specific IgE was positive; airway eosinophilic inflammation was observed. CONCLUSIONS TMA powder applied to the skin can lead to both immunologic sensitization and subsequent dose-dependent biphasic airway responses after TMA aerosol challenge.