Toxic epidermal necrolysis and Stevens-Johnson syndrome are severe blistering diseases generally considered to be hypersensitivity reaction to drugs. The aim of this study is to explore the diagnostic role of soluble Fas ligand secretion by peripheral blood mononuclear cells (PBMCs) in patients with previous drug-induced blistering diseases with or without stimulation with the offending drug. The results revealed that PBMCs from the patient group showed significant soluble Fas ligand secretion after stimulation with 100 microg/ml culprit drug (p<0.05). No significant change was seen in the control groups (p>0.05). Taken as a group, PBMCs from the patient group secreted more soluble Fas ligand than the normal control group regardless of drug stimulation. These results indicate that individuals whose PBMCs are high secretors of soluble Fas ligand are prone to severe toxic epidermal necrolysis/Stevens-Johnson syndrome. The possibility of using soluble Fas ligand secretion as a tool for retrospective determination of culprit drugs in patients with previous drug-induced blistering disease awaits further investigation.