The present review of the recent literature focuses on antigen-specific immune reactions in multiple sclerosis. New techniques have allowed precise quantitative analysis of the antigen-receptor repertoire of infiltrating T cells in the multiple sclerosis brain. Novel candidate autoantigens, including B-cell autoantigens, have been identified. 'Humanized' animal models allow the functional characterization of human immune molecules in vivo. Finally, several therapeutic trials have recently assessed the clinical benefit of selective immunotherapies.