Fas is a member of the tumor necrosis factor (TNF) family of proteins and has been implicated in an array of human diseases (e.g., various forms of hepatitis) resulting from inappropriate or excessive apoptosis-mediated cell death. On page 862, Zhang et al. describe the design, synthesis, and evaluation of a chemically modified 2′-O-(2-methoxy)ethyl antisense oligonucleotide (ISIS 22023) inhibitor of mouse Fas expression. Dosing with ISIS 22023 produced a 90% reduction in Fas mRNA and protein expression in the mouse liver model, affording complete protection from Fas antibody-induced fulminant hepatitis. Their results suggest the potential efficacy of oligonucleotide inhibitors of Fas in therapy for human liver disease.