Fas antigen and bcl-2 expression on peripheral blood mononuclear cells (PBMC) cultured with cytomegalovirus (CMV) and varicella-zoster virus (VZV) antigen was analyzed by three-color flow cytometry. Expression of Fas antigen increased significantly in CD45RO+ populations of both CD4+ and CD8+ cells obtained from CMV and VZV seropositive donors after culture with CMV and VZV antigen for 6 days. Fas antigen expression did not increase in PBMC cultured with control antigen. In contrast, bcl-2 expression decreased both in CD4+CD45RO+ and CD8+CD45RO+ cells from the same donors. Fas antigen and bcl-2 expression in CD45RA+ populations did not change. Cell viability of cultured cells with CMV and VZV antigen decreased after treatment with anti-Fas antibody and DNA fragments indicating apoptosis were detected in the cell lysate of these cultured cells after treatment with anti-Fas antibody. These data suggest that Fas antigen and bcl-2 protein may interact in regulating the cell death process of activated memory lymphocytes and eliminating lymphocytes activated by viral infection.