The present study was undertaken to investigate whether Epstein-Barr virus-(EBV) encoded latent membrane protein (LMP) induces the expression of BCL-2 in Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin's disease (HD) and thereby provide a possible mechanism for the role of EBV in the pathogenesis of this disease. Fifty-three cases of HD were studied for the presence of EBV using EBV-encoded RNA in situ hybridization and LMP immunohistochemistry. Immunostaining for BCL-2 on paraffin material was performed using microwave treatment of tissue sections before the application of the primary monoclonal antibody. EBV was located in HRS cells in 16 cases (30%). All cases that were EBV-encoded RNA in situ hybridization positive, also expressed LMP. BCL-2 expression in HRS cells was detected in 16 cases (30%), but only two of these were also EBV-positive. In both of these cases, only occasional HRS cells expressed BCL-2, in contrast to LMP, which was detected in nearly all such cells. BCL-2 staining was predominantly cytoplasmic with some membrane pattern. These results demonstrate that BCL-2 expression can be detected in HRS cells in routinely processed HD tissue and that whereas EBV does not induce the expression of BCL-2 in HD, BCL-2 may have a role in the pathogenesis of EBV-negative cases of HD.