Background: The mechanisms for the effectiveness of allergen immunotherapy (IT) are not well understood. The binding potential for immunoglobulins is a function of both antibody concentration and affinity (K(A)). Purpose: The purpose was to perform a cross-sectional preliminary study to investigate any differences in allergen-specific antibody affinity and concentration following ragweed immunotherapy by introducing a new concept of antibody binding capacity ([Ig] x K(A)). Methods: The binding capacity of allergen-specific IgE and IgG4 was determined for ragweed- allergic individuals undergoing ragweed immunotherapy and compared with the capacity of ragweed-specific IgE and IgG4 for allergic individuals not receiving immunotherapy. Results: The mean binding capacity for IgG4 after long-term immunotherapy was 1.6 log units higher (P < .0001) than for individuals not receiving IT. The binding capacity for allergen-specific IgE was 1.2 log units lower following long-term immunotherapy (P < .0001) compared with individuals not receiving ragweed IT. Conclusions: We hypothesize that a primary effect of immunotherapy is to increase IgG4 binding capacity and concomitantly decrease IgE binding capacity.