Tissues containing Hodgkin's disease (HD) are frequently infiltrated by large numbers of eosinophils. Because eosinophils as well as Reed- Sternberg (RS) cells express membrane receptors (CD23) for IgE, this study was performed to determine if IgE is present in tissue sections of HD and to correlate the results, when possible, with serum IgE levels and the presence of interleukin-5 (IL-5) messenger RNA (mRNA) in RS cells. Paraffin-embedded, B-5-fixed slices of 13 cases of HD, one case of acquired immunodeficiency syndrome (AIDS)-related HD, seven cases of benign lymphoid hyperplasia (including two cases from HD patients), and five cases of B-cell lymphomas were analyzed by a sensitive immunoperoxidase staining technique that used a murine monoclonal antibody specific for human IgE. In the benign hyperplastic lymph nodes and non-Hodgkin's lymphomas, IgE was generally detectable only in rare plasma cells and in follicular dendritic cells. In 11 of the 14 cases of HD, including one case of AIDS-related HD, IgE was readily detectable within RS cells and variants and on the surrounding cells and connective tissue. These cases also had significant numbers of eosinophils, and IL-5 mRNA was detectable in three of the cases that were tested. Serum IgE was moderately elevated in the two serum specimens from HD patients that were available for analysis. The results of this study, therefore, indicate that some cases of HD contain abundant deposits of IgE, which may account for the extensive infiltration by eosinophils seen in this neoplasm.