Background: Repeated dinitrochlorobenzene (DNCB) application has been proposed as a systemic immunotherapy on the basis of its ability to stimulate T helper 1 (T_H1) responses, such as those for systemic lupus erythematosus and HIV infection. Objective: We report the effect of topical DNCB therapy in an open trial in patients with refractory atopic dermatitis (AD). Methods: Eight patients with refractory AD received weekly application of 0.2% to 1% DNCB to a 2.5-cm² area on the upper arm after sensitization with 5% DNCB; the position was rotated at each application. Disease activity was monitored by pruritus score, percentage of body involvement, clinical severity score, eosinophil counts, serum IgE levels, and serum soluble interleukin 2 receptor levels. Results: Six of 8 patients (patients 1-6) showed apparent improvement both on clinical scores and laboratory data until 16 weeks after DNCB therapy (week 16). The clinical severity scores of patients 1 to 6 were significantly correlated with eosinophil counts, IgE levels, and serum soluble interleukin 2 receptor levels. One patient did not show clear improvement, and another (patient 8) showed deterioration. DNCB therapy was discontinued at week 12 for patient 8. Conclusion: Topical DNCB may systemically stimulate T_H1 cell responses of patients with AD, resulting in restoration of the T_H1/T_H2 imbalance and possible clinical improvement. These results, however, should be interpreted with caution until additional documentation is obtained. (J Am Acad Dermatol 2000;42:258-62.)