In order to determine whether IgE production occurs predominantly at mucosal or systemic sites, we studied the production of respiratory syncytial virus (RSV)-specific antibody in serum and nasopharyngeal secretions (NPS) from 41 patients with RSV infection using an enzyme-linked immunosorbent assay. RSV-IgE was found in higher titer in samples of NPS than in simultaneously obtained serum specimens at all phases of illness. Despite the excess dilution incurred in the collection process, RSV-IgE was frequently detected in NPS specimens while it was undetectable in serum. In 20 selected subjects, ratios of RSV antibody in NPS:serum were 2.00 for RSV-IgE, 2.42 for RSV-IgA, and 0.01 for RSV-IgG. Also the geometric mean value of ratios of RSV-IgE:RSV-IgG was 1.74 in NPS and 0.05 in serum, while the geometric mean value of ratios of RSV-IgA:RSV-IgG were 1.85 in NPS and 0.09 in serum. These data suggest that IgE production occurs predominantly at mucosal surfaces.