Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) leading to neurological deficits. The relative inaccessibility of the CNS for sampling and the problems of experimental manipulations in humans make proper experimental models indispensable for progress in the basic understanding of the disease as well as for testing of therapy. There is no single experimental model mimicking all aspects of MS and a model should be chosen based on the scientific question being investigated. We describe our experience with antigeninduced models in the rat species. The clinical course of disease, monophasic versus relapsing/protracted, and the histopathological features depend on the strain of rats used, their MHC and non-MHC genes, as well as the myelin autoantigen used for immunization. Other factors such as age, weight, and gender also influence the outcome. Use of myelin oligodendrocyte glycoprotein in DA rats results in an MS-like relapsing disease with plaques of demyelination. Use of myelin basic protein in LEW rats results in an acute monophasic inflammatory disease with little demyelination. Several disease-determining factors and practical schemes for MS models in rats are presented.