In spite of carrying large amount of Fas death receptor on the cell surface, Human T cell lymphotropic virus type-I (HTLV-I)infected T cell lines are resistant to Fas-mediated cytotoxicity. We investigated the mechanism(s) of HTLV-I-induced Fas resistancy. Western blotting and enzymatic activity analyses revealed that the Fas-elicited apoptotic signal in HTLV-I-infected T cells was intervened at the level(s) prior to the activation of caspase-8. Upon stimulation, the clustering of Fas receptors scarcely occurred in HTLV-I-infected cells. Cycloheximide treatment converted the resistant cells to sensitive cells, the presence of short-lived antiapoptotic molecule(s) that can block the caspase-8 activation within HTLV-I-infected T cells is suggested. (C) 2002 Elsevier Science (,USA). All rights reserved.