In addition to the full length mRNA activated human peripheral blood mononuclear cells (PBMC) and T cell tumor lines express several alternatively spliced Fas variants. At least five of these code for soluble Fas (CD95) molecules. In vitro studies suggest that these soluble Fas isoforms inhibit apoptosis induced by agonistic antibodies and, more importantly, by the natural Fas ligand in Fas-bearing sensitive cells. Interestingly, this functional property can be assigned to the first 49 aminoacids of the mature protein, the only region shared by the soluble Fas molecules.