Background: Atopic dermatitis (AD) is a chronic inflammatory dermatosis that probably involves a dysregulated activation of helper T cells, type 2 (Th2 cells). Severe refractory AD can be controlled by cyclosporine treatment. Objective: We attempted to determine whether short-term CD4 monoclonal antibody (mAb) therapy could improve severe AD in adults. Methods: The CD4 mAb, B-F5, was infused over 2 days in three patients with severe refractory AD and, for control purposes, in two patients with severe psoriasis. Results: Administration of B-F5 was well tolerated, despite moderate first dose side effects. Clinical improvement was observed in two patients. In the third patient, a dramatic worsening occurred between 8 and 30 days after treatment, associated with an increased percentage of activated CD4 + , CD25 + , HLA-DR + , and CD45RO + cells and peripheral blood eosinophilia. The same CD4 mAb administered to two patients with severe psoriasis induced marked clinical improvement of the lesions. Conclusion: Although CD4 mAb infusion may be potentially useful in the treatment of AD, the risk of aggravating the Th1/Th2 imbalance in AD should be considered in the design of future protocols. (J Am Acad Dermatol 1997;36:582-8.)