The present study demonstrates the cross-reactivity of a murine monoclonal antibody (MoAb) directed against purified ragweed antigen E (AgE) with human Ab1. This antiragweed AgE MoAb (clone SC7H.1G, IgM kappa) was used to detect Ab2 in the sera obtained from the three groups of subjects. Utilizing an ELISA assay, we found that immunoglobulins from 12 nonatopic subjects bound to a significantly greater extent to SC7H.1G (mean +/- SE; OD = 0.353 +/- 0.052) than immunoglobulins from 14 untreated ragweed atopics (OD = 0.149 +/- 0.020). However, immunoglobulins from 9 immunotherapy-treated patients (OD = 0.395 +/- 0.120) bound to the mouse anti-AgE MoAb to the same extent as nonatopic sera. Furthermore, an additional 7 patients with ragweed-allergic rhinitis were studied prospectively while undergoing immunotherapy and Ab2 levels were found to increase with time posttreatment. We also found an inverse correlation between Ab1 and Ab2 levels in the nonatopic and untreated atopic groups. These data indicate that immunotherapy stimulates the production of Ab2 in atopic patients and may be involved in the regulation of the antiragweed IgE response.