Background Atopic dermatitis (AD), a chronic inflammatory disorder, is often accompanied by allergic rhinoconjunctivitis (ARC) as a co‐morbidity. The use of a monoclonal anti‐IL‐4R α antibody has been effective in controlling moderate to severe AD symptoms. Allergen‐specific immunotherapy (AIT) is widely used for the treatment of ARC and asthma. The effects of AIT on basophil reactivity/effector functions have already been examined and used as indicators of the treatment efficacy. However, it is unclear, how an anti‐IL‐4R α antibody can influence allergen‐specific immune responses of basophils and T cells of AD patients with comorbid ARC. Objective To investigate the effect of a monoclonal anti‐IL‐4R α antibody on the in vitro allergic responses of basophils and T cells deriving from AD patients with comorbid ARC. Methods Blood samples of 32 AD patients were obtained before, after 4 and 16 weeks of an anti‐IL‐4R α antibody therapy (300 mg subcutaneously/2 weeks; n = 21) or AIT (daily sublingual application; n = 11). Patients treated with an anti‐IL‐4R α antibody were grouped according to their serum specific immunoglobulin E levels and ARC symptoms, while patients receiving an AIT were additionally grouped according to the allergen specificity of their AIT. Basophil activation test and T cell proliferation assays were undertaken after an in vitro allergen stimulation. Results A significant reduction of the immunoglobulin E levels and the allergen‐specific T cell proliferation was observed in AD patients treated with an anti‐IL‐4R α ‐ antibody, while the allergen‐specific basophil activation/sensitivity were found to be significantly increased. In patients receiving an AIT, the in vitro allergen‐specific basophil activation and the T cell proliferation were found to be significantly decreased in response to seasonal allergens. Conclusions An IL‐4R α blockade induced by a monoclonal anti‐IL‐4R α antibody leads to an increased activity/sensitivity of early effector cells (such as basophils), in contrast to a decreasing reactivity observed under an AIT. The late‐phase T cell reaction to allergens did not differ between the herein assessed treatments.