In the present transectional study, Fas ligand (Fas-L) levels, either in membrane or in soluble form, in cells from multiple sclerosis (MS) patients were investigated. Expression of Fas was evaluated after PHA stimulation of peripheral blood mononuclear cells from MS patients with relapsing-remitting or secondary-progressive disease, and in healthy donors. There was statistically significant decreased expression (p = 0.001), as well as release of Fas-L, (p = 0.045) in lymphocytes from MS patients, in comparison with healthy donors. Moreover, levels of Fas-L production were inversely correlated with the EDSS scores of patients in an highly significant way. Impairment of Fas-L release in stimulated PBMC from MS patients might influence the ability to eliminate autoreactive clones in vivo.