Using equimolar quantities of 2 chemical allergens, toluene diisocyanate (TDI), noted for its ability to cause respiratory hypersensitivity, and dinitrochlorobenzene (DNCB), noted for its dermal sensitizing activity, the mouse was evaluated as a possible model to indicate respiratory hypersensitivity. A previously published procedure (Garssen et al. (1989) Immunology 68, 51-58) was followed whereby chemicals were applied epicutaneously to the shaved flank of BALB/c mice. Eight days later, animals were challenged by intranasal application of the chemical. The lungs were evaluated at 48 h. Both TDI and DNCB elicited mild mononuclear inflammatory cuffing around pulmonary vasculature. No reaction was noted around pulmonary airways. Sera, drawn 48 h following the intranasal challenge with chemical allergen, were evaluated for total IgE, hapten-specific IgE and IgG, and for IL-2, IL-4, IL-5, IL-6, and interferon gamma. Animals exposed to TDI demonstrated decreased total IgE and the presence of TDI-specific IgG. Cytokine levels were unchanged in both groups. These results indicate that in this mouse model, total serum IgE and the production of hapten-specific IgG antibodies distinguished a respiratory from a contact sensitizing chemical. Further comparison of the serologic response of mice to these two classes of chemicals is required to determine if the murine model can be used to predict dermal versus respiratory sensitizing activity of chemical allergens.