To determine if Fas ligand (FasL) mediated apoptosis is involved in the pathogenesis of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we examined the expression of FasL mRNA in fresh uncultured peripheral blood mononuclear cells (PBMC) from 17 Japanese patients with HAM/TSP, four adult T-cell leukemia/lymphoma (ATL) patients, three asymptomatic HTLV-1 carriers and three normal individuals. Using competitive PCR with primers specific for FasL mRNA, we demonstrated that nine of 17 HAM/TSP and one of four ATL patients expressed significant levels of FasL mRNA, whereas asymptomatic carriers, normal controls and both HTLV-1 infected and uninfected T-cell lines did not. Cell separation analysis following PCR revealed that FasL mRNA was expressed in CD8 + T lymphocytes. FasL mRNA was preferentially expressed in patients with increased proviral load and longer duration of clinical illness. These results suggest that FasL mediated mechanisms contribute to the pathogenesis of HAM/TSP.