In the present study, we report that allogenic soluble HLA class I(sHLA-I) molecules isolated from serum induce apoptosis on EBV-specific CD8(+) Fas(+) cytotoxic T lymphocytes (CTL). CTL apoptosis is induced by thc binding of sHLA-I molecules to CD8 and its extent depends on the time of incubation with sHLA-I molecules. Apoptosis is triggered by the interaction of Fas(+) CTL with soluble Fas-ligand, which is released following che binding of sHLA-I antigens to CD8 molecules. These results suggest that sHLA-I molecules may regulate immune responses by inducing apoptosis in virus-specific CTL. (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.