Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the central nervous system (CNS) that shares clinical and pathophysiological feature with multiple sclerosis (MS) and is commonly used as an animal model for the human disease. Upon active immunization, different myelin proteins and other neuronal antigens are known to induce EAE in susceptible mouse strains. However, there are rodent strains reputed to be resistant to actively-induced EAE and the correct combination of animal strains and their respective autoantigen is absolutely critical as some antigens are encephalitogenic in one animal strain, but not in another. Here we describe actively-induced EAE in C3H/HeJ mice with different myelin peptides. Whereas no clinical signs could be found by immunization with myelin oligodendrocyte glycoprotein 35-55, significant weight loss as well as rapidly occurring severe ascending paralysis was found in animals immunized with proteolipid protein 190-209 (PLP(190-209)). Histologically, this form of EAE was characterized by predominant involvement of the spinal cord. As PLP is one of the major lipid antigens putatively involved in the pathogenesis of MS, this model may be useful for further studies of the disease.