Multiple sclerosis (MS) and other T cell-mediated autoimmune diseases develop in individuals carrying a complex susceptibility trait, probably following exposure to various environmental triggers. Owing to the presumed weak influence of single genes on disease predisposition and the recognized genetic heterogeneity of autoimmune disorders in humans, candidate gene searches in MS have been difficult. In an attempt to identify molecular markers indicative of disease status rather than susceptibility genes for MS, we show that gene expression profiling of peripheral blood mononuclear cells by cDNA microarrays can distinguish MS patients from healthy controls. Our findings support the concept that the activation of autoreactive T cells is of primary importance for this complex organ-specific disorder and prompt further investigations on gene expression in peripheral blood cells aimed at characterizing disease phenotypes.