The expression of the cell death-inducing protein, Bak, was investigated in 41 cases of Hodgkin's disease and was correlated with Epstein-Barr virus (EBV) status. Overall, Bak immunostaining was observed in 35/41 cases (85%). Among the 22 EBV-positive cases, 20 cases (91%) expressed Bak while 15/19 EBV-negative cases (79%) contained Bak-positive Reed-Sternberg cells. The expression of Bak, as assessed by the staining intensity and the numbers of positive tumor cells, varied greatly from case to case but was high in 6 cases (15%). Our findings show that, similar to Bax, a second apoptosis-inducing gene Bak is frequently expressed in Hodgkin's disease. Whilst Bak is suspected to protect cells immortalized by EBV from apoptosis, its expression in Hodgkin's disease appears to be unrelated to the EBV status of Reed-Sternberg cells. Moreover, the potential pro-apoptotic functions related to Bak and Bax in Hodgkin's disease might be surpassed by a stronger expression of anti-apoptotic molecules thus explaining tumor progression.