Respiratory and contact chemical allergens provoke differential immune responses in mice, stimulating preferentially T helper-2 (TH2) and TH1 cells, respectively. In an attempt to discover whether such differences are effected at the level of antigen handling and presentation we have examined the effect of topical exposure to trimellitic anhydride (TMA), a respiratory allergen, and 2,4-dinitrochlorobenzene (DNCB), a contact allergen, on Langerhans cell (LC) MHC class II (Ia) expression. Neither chemical caused a significant change in LC size. As measured by analytical flow cytometry, exposure to DNCB resulted in a time-dependent increase in LC Ia expression that exceeded 160% of control values within 24 h. Exposure to concentrations of TMA that caused an equivalent activation of draining lymph nodes failed to affect Ia expression by LC. Application of sodium lauryl sulfate at concentrations that caused edema also failed to influence LC Ia. These data demonstrate that TMA and DNCB exert differential effects on epidermal LC, possibly indicative of differences in antigen handling.